Jun. 2022, 東北大学医学部教室員会, 2021年度教室員会 The Best Teacher Awards　　　　　　　　　　　　　　　

Jun. 2021, 東北大学医学部教室員会, 2020年度教室員会 The Best Teacher Awards　　　　　　　　　　　　　　　

Jun. 2020, 東北大学医学部教室員会, 2019年度教室員会 The Best Teacher Awards　　　　　　　　　　　　　　　

15 Jan. 2016, 東北大学医学部, 東北大学医学部奨学賞 銀賞　　　　　　　　　　　　　　　
Others, Japan

16 May 2015, 公益財団法人 艮陵医学振興会, 平成27年度匂坂記念賞　　　　　　　　　　　　　　　
Publisher, Japan

Mar. 2014, 東北大学大学院医学系研究科, 平成25年度医学部・医学系研究科教育貢献賞　　　　　　　　　　　　　　　

19 Oct. 2012, 日本ヒスタミン学会, Young Investigator Award　　　　　　　　　　　　　　　
Japan society, Japan

Cystine transporter SLC7A11 regulates sensitivity to unsaturated carbonyl compounds in mouse macrophage cell lines
Tsunehito Higashi, Konoka Hashimoto, Yosuke Mai, Fumito Naganuma, Takeo Yoshikawa
Journal of Pharmacological Sciences, 157, 2, 96, 103, Elsevier BV, Feb. 2025, [Peer-reviewed], [Last author]
Scientific journal

Pharmacological inhibition of histamine N-methyltransferase extends wakefulness and suppresses cataplexy in a mouse model of narcolepsy
Fumito Naganuma, Birkan Girgin, Anne Bernadette S Agu, Kyosuke Hirano, Tadaho Nakamura, Kazuhiko Yanai, Ramalingam Vetrivelan, Takatoshi Mochizuki, Masashi Yanagisawa, Takeo Yoshikawa
SLEEP, Oxford University Press (OUP), 23 Oct. 2024, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal, Abstract

Histamine, a neurotransmitter, plays a predominant role in maintaining wakefulness. Further, our previous studies showed that histamine N-methyltransferase (HNMT), a histamine-metabolising enzyme, is important for regulating brain histamine concentration. However, the effects of pharmacological HNMT inhibition on mouse behaviour, including the sleep-wake cycle and cataplexy, in a mouse model of narcolepsy have not yet been investigated. In the present study, we investigated the effects of metoprine, an HNMT inhibitor with high blood-brain barrier permeability, in wild-type (WT) and orexin-deficient (OxKO) narcoleptic mice. Metoprine increased brain histamine concentration in a time- and dose-dependent manner without affecting peripheral histamine concentrations. Behavioural tests showed that metoprine increased locomotor activity in both novel and familiar environments, but did not alter anxiety-like behaviour. Sleep analysis showed that metoprine increased wakefulness and decreased non-rapid eye movement (NREM) sleep through the activation of the histamine H1 receptor (H1R) in WT mice. In contrast, the reduction of rapid eye movement (REM) sleep by metoprine occurred independent of H1R. In OxKO mice, metoprine was found to prolong wakefulness and robustly suppress cataplexy. In addition, metoprine has a greater therapeutic effect on cataplexy than pitolisant, which induces histamine release in the brain, and has been approved for patients with narcolepsy. These data demonstrate that HNMT inhibition has a strong effect on wakefulness, demonstrating therapeutic potential against cataplexy in narcolepsy.

Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus　　　　　　　　　　　　　　　
Fumito Naganuma, Mudasir Khanday, Sathyajit Sai Bandaru, Whidul Hasan, Kyosuke Hirano, Takeo Yoshikawa, Ramalingam Vetrivelan
Experimental Neurology, Oct. 2024, [Peer-reviewed]
English

MAST4 promotes primary ciliary resorption through phosphorylation of Tctex-1
Kensuke Sakaji, Sara Ebrahimiazar, Yasuhiro Harigae, Kenichi Ishibashi, Takeya Sato, Takeo Yoshikawa, Gen-ichi Atsumi, Ching-Hwa Sung, Masaki Saito
Life Science Alliance, 6, 11, e202301947, e202301947, Life Science Alliance, LLC, 19 Sep. 2023, [Peer-reviewed]
Scientific journal, The primary cilium undergoes cell cycle–dependent assembly and disassembly. Dysregulated ciliary dynamics are associated with several pathological conditions called ciliopathies. Previous studies showed that the localization of phosphorylated Tctex-1 at Thr94 (T94) at the ciliary base critically regulates ciliary resorption by accelerating actin remodeling and ciliary pocket membrane endocytosis. Here, we show that microtubule-associated serine/threonine kinase family member 4 (MAST4) is localized at the primary cilium. Suppressing MAST4 blocks serum-induced ciliary resorption, and overexpressing MAST4 accelerates ciliary resorption. Tctex-1 binds to the kinase domain of MAST4, in which the R503 and D504 residues are key to MAST4-mediated ciliary resorption. The ciliary resorption and the ciliary base localization of phospho-(T94)Tctex-1 are blocked by the knockdown of MAST4 or the expression of the catalytic-inactive site-directed MAST4 mutants. Moreover, MAST4 is required for Cdc42 activation and Rab5-mediated periciliary membrane endocytosis during ciliary resorption. These results support that MAST4 is a novel kinase that regulates ciliary resorption by modulating the ciliary base localization of phospho-(T94)Tctex-1. MAST4 is a potential new target for treating ciliopathies causally by ciliary resorption defects.

Epitope Mapping of Anti-Mouse CCR3 Monoclonal Antibodies (C3Mab-6 and C3Mab-7).
Nami Tateyama, Teizo Asano, Tomohiro Tanaka, Yu Isoda, Yuki Okada, Hiyori Kobayashi, Guanjie Li, Ren Nanamiya, Takeo Yoshikawa, Mika K Kaneko, Hiroyuki Suzuki, Yukinari Kato
Monoclonal antibodies in immunodiagnosis and immunotherapy, 42, 2, 68, 72, 18 Apr. 2023, [International Magazine]
English, Scientific journal, One of G protein-coupled receptors, CC chemokine receptor 3 (CCR3), is expressed in eosinophils, basophils, a subset of Th2 lymphocytes, mast cells, and airway epithelial cells. CCR3 levels in the serum of colorectal cancer patients are significantly higher than in control groups. Moreover, CCR3 is essential for recruiting eosinophils into the lung. Therefore, CCR3 is considered both a therapeutic target for colorectal cancer and allergic diseases. Previously, we established anti-mouse CCR3 (mCCR3) monoclonal antibodies (mAbs), C3Mab-6 (rat IgG1, kappa) and C3Mab-7 (rat IgG1, kappa), by immunizing a rat with an N-terminal peptide of mCCR3. These mAbs can be used in flow cytometry and enzyme-linked immunosorbent assays. In this study, we performed the epitope mapping of C3Mab-6 and C3Mab-7 using alanine scanning. The reactivity between these mAbs and point mutants of mCCR3 were analyzed using flow cytometry. The results indicated that Phe3, Asn4, Thr5, Asp6, Glu7, Lys9, Thr10, and Glu13 of mCCR3 are essential for C3Mab-6 binding, whereas Phe15 and Glu16 are essential for C3Mab-7 binding.

Epitope Mapping of the Novel Anti-Human CCR9 Monoclonal Antibody (C9Mab-11) by 2 × Alanine Scanning.
Yu Isoda, Tomohiro Tanaka, Hiroyuki Suzuki, Teizo Asano, Kaishi Kitamura, Yuma Kudo, Ryo Ejima, Kazuki Ozawa, Takeo Yoshikawa, Mika K Kaneko, Yukinari Kato
Monoclonal antibodies in immunodiagnosis and immunotherapy, 42, 2, 73, 76, Apr. 2023, [International Magazine]
English, Scientific journal, We recently developed a novel anti-human C-C chemokine receptor 9 (hCCR9) monoclonal antibody (mAb), C9Mab-11, which is applicable to flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA). This study aims to identify the binding epitope of C9Mab-11 by using 1 × and 2 × alanine (or glycine) substituted-hCCR9 peptides (1 × and 2 × Ala-scan) by ELISA. According to the 1 × Ala-scan analysis, the response of C9Mab-11 was diminished against M13A of the hCCR9 peptide, but was not eliminated. In the 2 × Ala-scan analysis, the reactions were abolished in the substitution of P11A-N12A, N12A-M13A, and M13A-A14G of hCCR9 N-terminal peptides. The results indicate that the binding epitope of C9Mab-11 includes Pro11, Asn12, Met13, and Ala14 of hCCR9, with the region around Met13 being particularly important. The successful identification of the C9Mab-11 epitope might be useful for the future pathophysiological analysis of hCCR9.

Epitope Mapping of an Anti-EpCAM Monoclonal Antibody (EpMab-37) Using the Alanine Scanning Method.
Guanjie Li, Hiroyuki Suzuki, Tomohiro Tanaka, Teizo Asano, Takeo Yoshikawa, Mika K Kaneko, Yukinari Kato
Monoclonal antibodies in immunodiagnosis and immunotherapy, 42, 1, 41, 47, Feb. 2023, [International Magazine]
English, Scientific journal, The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein, and plays critical roles in cell adhesion, proliferation, and tumorigenesis. EpCAM has been considered as a promising target for tumor diagnosis and therapy. Anti-EpCAM monoclonal antibodies (mAbs) have been developed for EpCAM-overexpressed tumors, and several clinical trials have demonstrated promising outcomes. We previously established an anti-EpCAM mAb, EpMab-37 (mouse IgG1, kappa), using the Cell-Based Immunization and Screening method. EpMab-37 was revealed to recognize the conformational epitope of EpCAM. In this study, we determined the critical epitope of EpMab-37 by flow cytometry using the 1 × alanine scanning (1 × Ala-scan) and the 2 × alanine scanning (2 × Ala-scan) method. We first performed flow cytometry by 1 × Ala-scan using one alanine (or glycine)-substituted EpCAM mutants, which were expressed on Chinese hamster ovary-K1 cells, and found that the EpMab-37 did not recognize the R163A mutant of EpCAM. We next performed flow cytometry by 2 × Ala-scan using two alanine (or glycine) residues-substituted EpCAM mutants, and confirmed that EpMab-37 did not recognize R163A-including mutants of EpCAM. The results indicated that the critical binding epitope of EpMab-37 includes Arg163 of EpCAM.

Antitumor activities of a defucosylated anti‑EpCAM monoclonal antibody in colorectal carcinoma xenograft models
Guanjie Li, Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Miyuki Yanaka, Takuro Nakamura, Takeo Yoshikawa, Manabu Kawada, Mika Kaneko, Yukinari Kato
International Journal of Molecular Medicine, 51, 2, Spandidos Publications, 18 Jan. 2023, [Peer-reviewed]
Scientific journal

Establishment of a Sensitive Monoclonal Antibody Against Mouse CCR9 (C₉Mab-24) for Flow Cytometry
Hiyori Kobayashi, Teizo Asano, Hiroyuki Suzuki, Tomohiro Tanaka, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 42, 1, 15, 21, Mary Ann Liebert Inc, 13 Dec. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The CC chemokine receptor 9 (CCR9), also known as CD199, is one of chemokine receptors. The CC chemokine ligand 25 (CCL25) is known to be the only ligand for CCR9. The CCR9-CCL25 interaction plays important roles in chemotaxis of lymphocytes and tumor cell migration. Therefore, CCR9-CCL25 axis is a promising target for tumor therapy and diagnosis. In this study, we established a sensitive and specific monoclonal antibody (mAb) against mouse CCR9 (mCCR9) using N-terminal peptide immunization method. The established anti-mCCR9 mAb, C9Mab-24 (rat immunoglobulin [IgG]2a, kappa), reacted with mCCR9-overexpressed Chinese hamster ovary-K1 (CHO/mCCR9) and mCCR9-endogenously expressed cell line, RL2, through flow cytometry. Kinetic analyses using flow cytometry showed that the dissociation constants (KD) of C9Mab-24 for CHO/mCCR9 and RL2 cell lines were 6.0 × 10-9 M and 4.7 × 10-10 M, respectively. Results indicated that C9Mab-24 is useful for detecting mCCR9 through flow cytometry, thereby providing a possibility for targeting mCCR9-expressing cells in vivo experiments.

Epitope Mapping of Anti-Mouse CCR3 Monoclonal Antibodies Using Flow Cytometry
Nami Tateyama, Teizo Asano, Hiroyuki Suzuki, Guanjie Li, Takeo Yoshikawa, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato
Antibodies, 11, 4, 75, 75, MDPI AG, 02 Dec. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The CC chemokine receptor 3 (CCR3) is a receptor for CC chemokines, including CCL5/RANTES, CCL7/MCP-3, and CCL11/eotaxin. CCR3 is expressed on the surface of eosinophils, basophils, a subset of Th2 lymphocytes, mast cells, and airway epithelial cells. CCR3 and its ligands are involved in airway hyperresponsiveness in allergic asthma, ocular allergies, and cancers. Therefore, CCR3 is an attractive target for those therapies. Previously, anti-mouse CCR3 (mCCR3) monoclonal antibodies (mAbs), C3Mab-3 (rat IgG2a, kappa), and C3Mab-4 (rat IgG2a, kappa) were developed using the Cell-Based Immunization and Screening (CBIS) method. In this study, the binding epitope of these mAbs was investigated using flow cytometry. A CCR3 extracellular domain-substituted mutant analysis showed that C3Mab-3, C3Mab-4, and a commercially available mAb (J073E5) recognized the N-terminal region (amino acids 1–38) of mCCR3. Next, alanine scanning was conducted in the N-terminal region. The results revealed that the Ala2, Phe3, Asn4, and Thr5 of mCCR3 are involved in C3Mab-3 binding, whereas Ala2, Phe3, and Thr5 are essential to C3Mab-4 binding, and Ala2 and Phe3 are crucial to J073E5 binding. These results reveal the involvement of the N-terminus of mCCR3 in the recognition of C3Mab-3, C3Mab-4, and J073E5.

A Defucosylated Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity in Xenograft Model
Teizo Asano, Tomohiro Tanaka, Hiroyuki Suzuki, Guanjie Li, Tomokazu Ohishi, Manabu Kawada, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Antibodies, 11, 4, 74, 74, MDPI AG, 24 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti-EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against a breast cancer cell line (BT-474) and a pancreatic cancer cell line (Capan-2), both of which express EpCAM. EpMab-37-mG2a-f recognized BT-474 and Capan-2 cells with a moderate binding-affinity [apparent dissociation constant (KD): 2.9 × 10−8 M and 1.8 × 10−8 M, respectively] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for both cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities and could provide valuable therapeutic regimen for breast and pancreatic cancers.

Defucosylated Mouse-Dog Chimeric Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody (H77Bf) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma
Ren Nanamiya, Tomokazu Ohishi, Hiroyuki Suzuki, Takuya Mizuno, Takeo Yoshikawa, Teizo Asano, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 42, 1, 27, 33, Mary Ann Liebert Inc, 18 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Human epidermal growth factor receptor 2 (HER2) has been studied in many human cancer types, and its overexpression and/or gene mutation contribute to the poor prognosis. Therefore, HER2 is an important therapeutic target in various cancer types, including breast and gastric cancers. We previously developed an anti-HER2 monoclonal antibody (mAb), H2Mab-77 (mouse IgG1, kappa), which detects HER2 and dog HER2 (dHER2) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-HER2 mAb (H77Bf), and investigated the reactivity against canine osteosarcoma D-17 cells by flow cytometry. Furthermore, we showed that H77Bf exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells in vitro and exhibited the potent antitumor activity in vivo. These results suggest that H77Bf exerts antitumor effects against dHER2-expressing canine tumors and could be valuable as part of an antibody treatment regimen for them.

Antitumor Activity of an Anti-EGFR/HER2 Bispecific Antibody in a Mouse Xenograft Model of Canine Osteosarcoma
Nami Tateyama, Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Takuya Mizuno, Takeo Yoshikawa, Manabu Kawada, Mika K. Kaneko, Yukinari Kato
Pharmaceutics, 14, 11, 2494, 2494, MDPI AG, 17 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The overexpression of epidermal growth factor receptors (EGFRs) has been reported in various human tumors, including breast, gastric, lung, colorectal, and pancreatic cancers. Humanized anti-EGFR and anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies (mAbs) have been shown to improve patients’ survival. Canine tumors resemble human tumors in the initiation and progression. We previously established a defucosylated mouse-dog chimeric anti-EGFR mAb (E134Bf) and a mouse-dog chimeric anti-HER2 mAb (H77Bf), which exerted antitumor activities in canine tumor xenograft models. Here, we produced E134Bf antibody fused to H77Bf single chain Fv at the light chains (E134Bf-H77scFv). The bispecific E134Bf-H77scFv recognized dog EGFR (dEGFR) and dog HER2 (dHER2)-overexpressed Chinese hamster ovary-K1 cells by flow cytometry. E134Bf-H77scFv also reacted with dEGFR/dHER2-positive canine osteosarcoma D-17 cells, and possesses a high binding-affinity (KD: 1.3 × 10−9 M). Furthermore, E134Bf-H77scFv exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells in the presence of canine mononuclear cells and complement, respectively. Moreover, administration of E134Bf-H77scFv suppressed the development of D-17 xenograft tumor in mice early compared with the control dog IgG, E134Bf and H77Bf alone. These results indicate that E134Bf-H77scFv exerts antitumor activities against dEGFR/dHER2-positive canine tumors, and could be a valuable treatment regimen for canine tumors.

Development of a Novel Anti-Mouse CCR6 Monoclonal Antibody (C₆Mab-13) by N-Terminal Peptide Immunization
Teizo Asano, Tomohiro Tanaka, Hiroyuki Suzuki, Guanjie Li, Ren Nanamiya, Nami Tateyama, Yu Isoda, Yuki Okada, Hiyori Kobayashi, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 41, 6, 343, 349, Mary Ann Liebert Inc, 16 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The CC chemokine receptor 6 (CCR6) is a G protein-coupled receptor family member that is highly expressed in B lymphocytes, certain subsets of effector and memory T cells, and immature dendritic cells. CCR6 has only one chemokine ligand, CCL20. The CCL20-CCR6 axis has been recognized as a therapeutic target for autoimmune diseases and tumor. This study developed specific monoclonal antibodies (mAbs) against mouse CCR6 (mCCR6) using the peptide immunization method. The established anti-mCCR6 mAb, C6Mab-13 (rat IgG1, kappa), reacted with mCCR6-overexpressed Chinese hamster ovary-K1 (CHO/mCCR6), and mCCR6-endogenously expressed P388 (mouse lymphoid neoplasma) and J774-1 (mouse macrophage-like) cells in flow cytometry. The dissociation constant (KD) of C6Mab-13 for CHO/mCCR6 cells was determined to be 2.8 × 10-9 M, indicating that C6Mab-13 binds to mCCR6 with high affinity. In summary, C6Mab-13 is useful for detecting mCCR6-expressing cells through flow cytometry.

Antitumor Activities in Mouse Xenograft Models of Canine Fibroblastic Tumor by Defucosylated Mouse-Dog Chimeric Anti-HER2 Monoclonal Antibody (H77Bf)
Hiroyuki Suzuki, Teizo Asano, Tomokazu Ohishi, Takeo Yoshikawa, Hiroyoshi Suzuki, Takuya Mizuno, Tomohiro Tanaka, Manabu Kawada, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 42, 1, 34, 40, Mary Ann Liebert Inc, 16 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Human epidermal growth factor receptor 2 (HER2) is a cell surface type I transmembrane glycoprotein that is overexpressed on a variety of solid tumors and transduces the oncogenic signaling upon homo- and heterodimerization with HER families. Anti-HER2 monoclonal antibodies (mAbs) including trastuzumab and its antibody-drug conjugate have been shown to improve patients' survival in HER2-positive breast, gastric, and lung cancers. Canine tumors have advantages as naturally occurring tumor models, and share biological and histological characteristics with human tumors. In this study, we generated a defucosylated version of mouse-dog chimeric anti-HER2 mAb (H77Bf) derived from H2Mab-77 (mouse IgG1, kappa). H77Bf possesses the high binding affinity (a dissociation constant: 8.7 × 10-10 M) for a dog HER2 (dHER2)-expressing canine fibroblastic tumor cell line (A-72). H77Bf exhibited antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity for A-72 cells. Moreover, intraperitoneal administration of H77Bf significantly suppressed the development of A-72 tumor compared with the control dog IgG in a mouse xenograft model. These results indicate that H77Bf exerts antitumor activities against dHER2-expressing canine cancers, which could provide a valuable information for canine cancer treatment.

Development of a Sensitive Anti-Human CCR9 Monoclonal Antibody (C₉Mab-11) by N-Terminal Peptide Immunization
Tomohiro Tanaka, Hiroyuki Suzuki, Yu Isoda, Teizo Asano, Takuro Nakamura, Miyuki Yanaka, Saori Handa, Nozomi Takahashi, Saori Okuno, Takeo Yoshikawa, Guanjie Li, Ren Nanamiya, Nohara Goto, Nami Tateyama, Yuki Okada, Hiyori Kobayashi, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 41, 6, 303, 310, Mary Ann Liebert Inc, 16 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The C-C chemokine receptor 9 (CCR9) belongs to the G-protein-coupled receptor superfamily, and is highly expressed on the T cells and intestinal cells. CCR9 regulates various immune responses by binding to the C-C chemokine ligand, CCL25, and is involved in inflammatory diseases and tumors. Therefore, the development of sensitive monoclonal antibodies (mAbs) for CCR9 is necessary for treatment and diagnosis. In this study, we established a specific anti-human CCR9 (hCCR9) mAb; C9Mab-11 (mouse IgG2a, kappa), using the synthetic peptide immunization method. C9Mab-11 reacted with hCCR9-overexpressed Chinese hamster ovary-K1 (CHO/hCCR9) and hCCR9-endogenously expressed MOLT-4 (human T-lymphoblastic leukemia) cells in flow cytometry. The dissociation constant (KD) of C9Mab-11 for CHO/hCCR9 and MOLT-4 cells were determined to be 1.2 × 10-9 M and 4.9 × 10-10 M, respectively, indicating that C9Mab-11 possesses a high affinity for both exogenously and endogenously hCCR9-expressing cells. Furthermore, C9Mab-11 clearly detected hCCR9 protein in CHO/hCCR9 cells using western blot analysis. In summary, C9Mab-11 can be a useful tool for analyzing hCCR9-related biological responses.

Epitope Mapping Using the Cell-Based 2 × Alanine Substitution Method About the Anti-mouse CXCR6 Monoclonal Antibody, Cx₆Mab-1
Yu Isoda, Tomohiro Tanaka, Hiroyuki Suzuki, Teizo Asano, Takeo Yoshikawa, Kaishi Kitamura, Yuma Kudo, Ryo Ejima, Kazuki Ozawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 42, 1, 22, 26, Mary Ann Liebert Inc, 16 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, An anti-mouse CXC chemokine receptor 6 (mCXCR6) monoclonal antibody (mAb), Cx6Mab-1, was developed recently. Cx6Mab-1 is applicable for flow cytometry, Western blotting, and enzyme-linked immunosorbent assay. The purpose of this study is to determine the binding epitope of Cx6Mab-1 using 2 × alanine mutated mCXCR6. Analysis of flow cytometry revealed that Cx6Mab-1 did not recognize S8A-A9G, L10A-Y11A, D12A-G13A, and H14A-Y15A mutants of mCXCR6. The results clearly indicate that the binding epitope of Cx6Mab-1 includes Ser8, Ala9, Leu10, Tyr11, Asp12, Gly13, His14, and Tyr15 of mCXCR6. The successful determination of the Cx6Mab-1 epitope might contribute to the pathophysiological investigation of mCXCR6.

Epitope Mapping of an Anti-Mouse CCR2 Monoclonal Antibody (C₂Mab-6) Using Enzyme-Linked Immunosorbent Assay
Tomohiro Tanaka, Hiroyuki Suzuki, Teizo Asano, Guanjie Li, Ren Nanamiya, Nami Tateyama, Yu Isoda, Yuki Okada, Hiyori Kobayashi, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 41, 6, 339, 342, Mary Ann Liebert Inc, 07 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, CC chemokine receptor type-2 (CCR2) is a member of the G protein-coupled receptors, and is mainly expressed on cell surface of immune cells. CCR2 binds to its ligand, C-C motif chemokine 2 (also named as monocyte chemoattractant protein-1), which involves in the tumor progression by modulating the tumor microenvironment. Therefore, the monoclonal antibody (mAb) targeting CCR2 could be one of the strategies for cancer treatment. In this study, we investigated the critical epitope of C2Mab-6, an anti-mouse CCR2 (mCCR2) mAb developed by N-terminal peptides immunization. We first performed enzyme-linked immunosorbent assay (ELISA) using N-terminal peptides of mCCR2 and demonstrated that C2Mab-6 recognizes 1-19 amino acids of mCCR2. We further performed ELISA using 20 alanine-substituted peptides of mCCR2. C2Mab-6 lost the reaction to the alanine-substituted peptides of D3A, N4A, M6A, P8A, Q9A, and F10A. These results indicate that the binding epitope of C2Mab-6 includes Asp3, Asn4, Met6, Pro8, Gln9, and Phe10 of mCCR2.

KLMab-1: An Anti-human KLRG1 Monoclonal Antibody for Immunocytochemistry
Masaki Saito, Hiroyuki Suzuki, Teizo Asano, Tomohiro Tanaka, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 41, 5, 279, 284, Mary Ann Liebert Inc, 28 Oct. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Immune checkpoint molecules have received attention as targets of cancer immunotherapy. Killer cell lectin-like receptor subfamily G member 1 (KLRG1) is one of the immune checkpoint molecules expressed in CD4+ T, CD8+ T, and natural killer (NK) cells. KLRG1 exhibits antiviral and antitumor immunity, and its expression in T and NK cells is upregulated by viral infectious diseases and some tumors. Thus, monoclonal antibodies (mAbs) for KLRG1 would be useful tools for the diagnosis and immunotherapy against viral infectious diseases and cancers. We have developed anti-human KLRG1 (hKLRG1) mAb (clone KLMab-1, mouse IgG1, kappa) by the Cell-Based Immunization and Screening method. We have also demonstrated that KLMab-1 recognizes both exogenous and endogenous hKLRG1 in flow cytometry. In this study, we first showed that KLMab-1 and its recombinant mAb (recKLMab-1) bound to exogenous hKLRG1 overexpressed in Chinese hamster ovary (CHO)-K1 cells, but not in parental CHO-K1 cells, in immunocytochemistry. We next showed that both mAbs detected endogenous hKLRG1 expressed in human NK cells. These results demonstrate that KLMab-1 and recKLMab-1 are available for immunocytochemistry.

Epitope Mapping of an Anti-Mouse CXCR6 Monoclonal Antibody (Cx₆Mab-1) Using the 2 × Alanine Scanning Method
Yu Isoda, Tomohiro Tanaka, Hiroyuki Suzuki, Teizo Asano, Takuro Nakamura, Miyuki Yanaka, Saori Handa, Yu Komatsu, Saori Okuno, Nozomi Takahashi, Yuki Okada, Hiyori Kobayashi, Guanjie Li, Ren Nanamiya, Nohara Goto, Nami Tateyama, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 41, 5, 275, 278, Mary Ann Liebert Inc, 25 Oct. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The CXC chemokine receptor 6 (CXCR6) is a member of the G protein-coupled receptor family that is highly expressed in helper T type 1 cells, cytotoxic T lymphocytes (CTLs), and natural killer cells. CXCR6 plays critical roles in local expansion of effector-like CTLs in tumor microenvironment to potentiate the antitumor response. Therefore, the development of anti-CXCR6 monoclonal antibodies (mAbs) is essential to evaluate the immune microenvironment of tumors. Using N-terminal peptide immunization, we previously developed an anti-mouse CXCR6 (mCXCR6) mAb, Cx6Mab-1 (rat IgG1, kappa) , which is useful for flow cytometry and western blotting. In this study, we determined the critical epitope of Cx6Mab-1 by enzyme-linked immunosorbent assay (ELISA) using the 1 × alanine scanning (1 × Ala-scan) method or the 2 × alanine scanning (2 × Ala-scan) method. Although we first performed ELISA by 1 × Ala-scan using one alanine-substituted peptides of mCXCR6 N-terminal domain (amino acids 1-20), we could not identify the Cx6Mab-1 epitope. We next performed ELISA by 2 × Ala-scan using two alanine (or glycine) residues-substituted peptides of mCXCR6 N-terminal domain, and found that Cx6Mab-1 did not recognize S8A-A9G, A9G-L10A, L10A-Y11A, and G13A-H14A of the mCXCR6 N-terminal peptide. The results indicate that the binding epitope of Cx6Mab-1 includes Ser8, Ala9, Leu10, Tyr11, Gly13, and His14 of mCXCR6. Therefore, we could demonstrate that the 2 × Ala scan method is useful for determining the critical epitope of mAbs.

Epitope Mapping of the Anti-Human CC Chemokine Receptor Type-2 Monoclonal Antibody (K036C2)
Tomohiro Tanaka, Hiroyuki Suzuki, Guanjie Li, Ren Nanamiya, Yu Isoda, Yuki Okada, Hiyori Kobayashi, Takeo Yoshikawa, Mika K. Kaneko, Yukinari Kato
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 41, 5, 285, 289, Mary Ann Liebert Inc, 25 Oct. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, CC chemokine receptor type-2 (CCR2) belongs to the G protein-coupled receptors superfamily, and is localized on cell surface of tumor cells and some immune cells, including monocytes and macrophages. CCR2 is a receptor for monocyte chemoattractant protein-1/C-C motif chemokine 2, and is involved in the progression of various diseases such as cancers. Therefore, the development of CCR2-targeted monoclonal antibody (mAb) is desired. Its characterization, including epitope of mAb, is very important for antibody applications. In this study, we investigated the critical epitope of K036C2, which is a commercially available anti-human CCR2 (hCCR2) mAb. We conducted enzyme-linked immunosorbent assay (ELISA) using three N-terminal peptides of hCCR2 and demonstrated that K036C2 recognizes 11-29 and 21-39 amino acids of hCCR2. We further performed ELISA using 20 peptides, which include alanine substitution of hCCR2. K036C2 lost the reaction to the alanine-substituted peptides of D25A, Y26A, D27A, G29A, and A30G. These results indicate that the critical binding epitope of K036C2 includes Asp25, Tyr26, Asp27, Gly29, and Ala30 of hCCR2.

Defucosylated mouse‑dog chimeric anti‑HER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors
Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Masaki Saito, Takuya Mizuno, Takeo Yoshikawa, Manabu Kawada, Mika Kaneko, Yukinari Kato
Oncology Reports, 48, 3, Spandidos Publications, 15 Jul. 2022
Scientific journal

Oral histidine intake improves working memory through the activation of histaminergic nervous system in mice
Tadaho Nakamura, Fumito Naganuma, Uta Kudomi, Sueji Roh, Kazuhiko Yanai, Takeo Yoshikawa
Biochemical and Biophysical Research Communications, 609, 141, 148, Elsevier BV, Jun. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Histamine is synthesised from l-histidine through the catalysis of histidine decarboxylase (HDC). In the central nervous system (CNS), histamine is exclusively produced in histaminergic neurons located in the posterior hypothalamus and controls various CNS functions. Although histidine was known as a precursor of histamine, the impact of oral histidine intake on brain histamine concentration and brain function has not been fully elucidated. In the present study, we aimed to elucidate the importance of oral histidine supplementation in the histaminergic nervous system and working memory in stressful conditions. First, we confirmed that sleep deprivation by water-floor stress in male mice increased histamine consumption and resulted in histamine reduction and impaired working memory in the Y-maze test. This memory impairment was rescued by intracerebroventricular injection of histamine and histidine, indicating that oral histidine intake could also improve memory function. Next, we examined the impact of histidine intake on brain histamine concentration and neuronal activity. Histidine intake increased extracellular histamine concentration around the prefrontal cortex (PFC) and the basal forebrain (BF), leading to a robust increase in the number of c-fos-positive cells around these areas. Finally, we investigated the beneficial effects of histidine intake on working memory. Histidine supplementation alleviated impaired memory function induced by sleep deprivation. This beneficial effect of histidine on memory was cancelled by intracerebroventricular injection of the HDC inhibitor α-fluoromethylhistidine. These results demonstrate that oral histidine intake replenishes brain histamine and leads to the recovery of impaired working memory induced by sleep deprivation through histaminergic activation.

Histamine and Microglia.
Tomomitsu Iida, Kazuhiko Yanai, Takeo Yoshikawa
Current topics in behavioral neurosciences, 59, 241, 259, 11 May 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Microglia, a category of glial cells in the central nervous system (CNS), have attracted much attention because of their important role in neuroinflammation. Many translational studies are currently ongoing to discover novel drugs targeting microglia for the treatment of various CNS disorders, such as Alzheimer's disease, Parkinson's disease (PD), and depression. Recent studies have shown that brain histamine, a neurotransmitter essential for the regulation of diverse brain functions, controls glial cells and neurons. In vitro studies using primary microglia and microglial cell lines have reported that histamine receptors are expressed in microglia and control microglial functions, including chemotaxis, migration, cytokine secretion, and autophagy. In vivo studies have demonstrated that histamine-related reagents could ameliorate abnormal symptoms in animal models of human diseases, such as amyotrophic lateral sclerosis (ALS), PD, and brain ischemia. Several human studies have revealed alterations in histamine receptor levels in ALS and PD, emphasizing the importance of the CNS histamine system, including histamine-dependent microglial modulation, as a therapeutic target for these disorders. In this review article, we summarize histamine-related research focusing on microglial functions.

Contribution of astrocytic histamine N-methyltransferase to histamine clearance and brain function in mice.
Rina Otsuka, Fumito Naganuma, Tadaho Nakamura, Hideki Miwa, Rumi Nakayama-Naono, Takuro Matsuzawa, Yurika Komatsu, Yuki Sato, Yuna Takahashi, Haruna Tatsuoka-Kitano, Kazuhiko Yanai, Takeo Yoshikawa
Neuropharmacology, 212, 109065, 109065, 26 Apr. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Brain histamine acts as a neurotransmitter in the regulation of various brain activities. Previous studies have shown that histamine N-methyltransferase (HNMT), a histamine-metabolizing enzyme, controls brain histamine concentration and brain function. However, the relative contribution of astrocytic or neuronal HNMT to the regulation of the histaminergic system is still inconclusive. Here, we phenotyped astrocytes-specific HNMT knockout (cKO) mice to clarify the involvement of astrocytic HNMT in histamine clearance and brain function. First, we performed histological examinations using HNMT reporter mice and showed a wide distribution of HNMT in the brain and astrocytic HNMT expression. Then, we created cKO mice by Cre-loxP system and confirmed that HNMT expression in cKO primary astrocytes was robustly decreased. Although total HNMT level in the cortex was not substantially different between control and cKO brains, histamine concentration after histamine release was elevated in cKO cortex. In behavioral tests, impaired motor coordination and lower locomotor activity were observed in the cKO mice. However, anxiety-like behaviors, depression-like behaviors, and memory functions were not altered by astrocytic HNMT disruption. Although sleep analysis demonstrated that the quantity of wakefulness and sleep did not change, the increased power density of delta frequency during wakefulness indicated lower cortical activation in cKO mice. These results demonstrate that astrocytic HNMT contributes to histamine clearance after histamine release in the cortex and plays a role in the regulation of motor coordination, locomotor activity, and vigilance state.

【With/afterコロナ時代の新たな薬理学教育I:遠隔教育の実践と課題】オンライン薬理学ロールプレイの実践と課題
中村 正帆, 吉川 雄朗, 柳田 俊彦, 岡村 信行, 谷内 一彦
日本薬理学雑誌, 156, 6, 338, 344, (公社)日本薬理学会, Nov. 2021
Japanese

Efficacy and Safety of Non-brain Penetrating H1-Antihistamines for the Treatment of Allergic Diseases.
Kazuhiko Yanai, Takeo Yoshikawa, Martin K Church
Current topics in behavioral neurosciences, 59, 193, 214, 08 Oct. 2021, [International Magazine]
English, Scientific journal, H1 receptor antagonists, known as H1-antihistamines (AHs), inactivate the histamine H1-receptor thereby preventing histamine causing the primary symptoms of allergic diseases, such as atopic dermatitis, pollinosis, food allergies, and urticaria. AHs, which are classified into first-generation (fgAHs) and second-generation (sgAHs) antihistamines, are the first line of treatment for allergic diseases. Although fgAHs are effective, they cause adverse reactions such as potent sedating effects, including drowsiness, lassitude, and cognitive impairment; anticholinergic effects, including thirst and tachycardia. Consequently, the use of fgAHs is not recommended for allergic diseases. Today, sgAHs, which are minimally sedating and, therefore, may be used at more effective doses, are the first-line treatment for alleviating the symptoms of allergic diseases. Pharmacologically, the use of sedating fgAHs is limited to antiemetics, anti-motion sickness drugs, and antivertigo drugs. The use of histamine H1-receptor occupancy (H1RO) based on positron emission tomography (PET) has been developed for the evaluation of brain penetrability. Based on the results of the H1RO-PET studies, non-brain-penetrating AHs (nbpAHs) have recently been reclassified among sgAHs. The nbpAHs are rapidly acting and exhibit minimal adverse reactions and, thus, are considered first-line drugs for allergic diseases. In this review, we will introduce recent topics on the pharmacodynamics and pharmacokinetics of AHs and make recommendations for the use of nbpAHs as first-line treatment options for allergic diseases.

Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness.
Fumito Naganuma, Tadaho Nakamura, Hiroshi Kuroyanagi, Masato Tanaka, Takeo Yoshikawa, Kazuhiko Yanai, Nobuyuki Okamura
Scientific reports, 11, 1, 17935, 17935, 09 Sep. 2021, [International Magazine]
English, Scientific journal, Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomamillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep-wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep-wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident-intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 h. These changes in wakefulness induced by HATMN modulation were related to the maintenance of vigilance state. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.

Heparan sulfate promotes differentiation of white adipocytes to maintain insulin sensitivity and glucose homeostasis.
Takuro Matsuzawa, Masanobu Morita, Ai Shimane, Rina Otsuka, Yu Mei, Fumitoshi Irie, Yu Yamaguchi, Kazuhiko Yanai, Takeo Yoshikawa
The Journal of biological chemistry, 297, 3, 101006, 101006, 23 Jul. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Heparan sulfate (HS), a highly sulfated linear polysaccharide, is involved in diverse biological functions in various tissues. Although previous studies have suggested a possible contribution of HS to the differentiation of white adipocytes, there has been no direct evidence supporting this. Here, we inhibited the synthesis of HS chains in 3T3-L1 cells using CRISPR/Cas9 technology, resulting in impaired differentiation of adipocytes with attenuated BMP4 (bone morphogenetic protein 4)/FGF1 (fibroblast growth factor 1) signaling pathways. HS reduction resulted in reduced glucose uptake and decreased insulin-dependent intracellular signaling. We then made heterozygous mutant mice for the Ext1 gene, which encodes an enzyme essential for the HS biosynthesis, specifically in the visceral white adipose tissue (Fabp4-Cre+::Ext1flox/WT mice, hereafter called Ext1Δ/WT) to confirm the importance of HS in vivo. The expression levels of transcription factors that control adipocyte differentiation, such as peroxisome proliferator-activated receptor gamma, were reduced in Ext1Δ/WT adipocytes, which contained smaller, unilocular lipid droplets, reduced levels of enzymes involved in lipid synthesis, and altered expression of BMP4/FGF1 signaling molecules. Further, we examined the impact of HS reduction in visceral white adipose tissue on systemic glucose homeostasis. We observed that Ext1Δ/WT mice showed glucose intolerance due to insulin resistance. Our results demonstrate that HS plays a crucial role in the differentiation of white adipocytes through BMP4/FGF1 signaling pathways, thereby contributing to insulin sensitivity and glucose homeostasis.

臨床化学に寄与する糖鎖科学の進展 ブドウ糖代謝におけるヘパラン硫酸の重要性について
松澤 拓郎, 谷内 一彦, 吉川 雄朗
日本臨床検査医学会誌, 69, 6, 451, 457, (一社)日本臨床検査医学会, Jun. 2021
Japanese

膵β細胞におけるグルコース応答性転写因子ChREBPの機能制御因子の探索　　　　　　　　　　　　　　　
横山 敦, 野呂 英理香, 岡本 好司, 松澤 拓郎, 吉川 雄朗, 島 弘季, 五十嵐 和彦, 菅原 明
日本内分泌学会雑誌, 97, 1, 319, 319, (一社)日本内分泌学会, Apr. 2021
Japanese

Organic Cation Transporters in Brain Histamine Clearance: Physiological and Psychiatric Implications.
Fumito Naganuma, Takeo Yoshikawa
Handbook of experimental pharmacology, 266, 169, 185, 28 Feb. 2021, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Histamine acts as a neurotransmitter in the central nervous system and is involved in numerous physiological functions. Recent studies have identified the causative role of decreased histaminergic systems in various neurological disorders. Thus, the brain histamine system has attracted attention as a therapeutic target to improve brain function. Neurotransmitter clearance is one of the most important processes for the regulation of neuronal activity and is an essential target for diverse drugs. Our previous study has shown the importance of histamine N-methyltransferase for the inactivation of brain histamine and the intracellular localization of this enzyme; the study indicated that the transport system for the movement of positively charged histamine from the extracellular to intracellular space is a prerequisite for histamine inactivation. Several studies on in vitro astrocytic histamine transport have indicated the contribution of organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) in histamine uptake, although the importance of these transporters in in vivo histamine clearance remains unknown. Immunohistochemical analyses have revealed the expression of OCT3 and PMAT on neurons, emphasizing the importance of investigating neuronal histamine uptake. Further studies using knockout mice or fast-scan cyclic voltammetry will accelerate the research on histamine transporters. In this review article, we summarize histamine transport assays and describe the candidate transporters responsible for histamine transport in the brain.

Histaminergic neurons in the tuberomammillary nucleus as a control centre for wakefulness
Takeo Yoshikawa, Tadaho Nakamura, Kazuhiko Yanai
British Journal of Pharmacology, 178, 4, 750, 769, Wiley, Feb. 2021, [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Histamine plays pleiotropic roles as a neurotransmitter in the physiology of brain function, this includes the maintenance of wakefulness, appetite regulation and memory retrieval. Since numerous studies have revealed an association between histaminergic dysfunction and diverse neuropsychiatric disorders, such as Alzheimer's disease and schizophrenia, a large number of compounds acting on the brain histamine system have been developed to treat neurological disorders. In 2016, pitolisant, which was developed as a histamine H3 receptor inverse agonist by Schwartz and colleagues, was launched for the treatment of narcolepsy, emphasising the prominent role of brain histamine on wakefulness. Recent advances in neuroscientific techniques such as chemogenetic and optogenetic approaches have led to remarkable progress in the understanding of histaminergic neural circuits essential for the control of wakefulness. In this review article, we summarise the basic knowledge about the histaminergic nervous system and the mechanisms underlying sleep/wake regulation that are controlled by the brain histamine system. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.4/issuetoc.

The development of online role-play for pharmacological education
Tadaho Nakamura, Takeo Yoshikawa, Toshihiko Yanagita, Nobuyuki Okamura, Kazuhiko Yanai
Folia Pharmacologica Japonica, 156, 6, 338, 344, Japanese Pharmacological Society, 2021
Japanese, Scientific journal

【COVID-19パンデミック下での薬学教育〜レジリエントな教育システム構築に向けて〜】医学・薬学・歯学教育におけるオンラインロールプレイを活用した実践的薬物治療教育の試み　　　　　　　　　　　　　　　
柳田 俊彦, 中村 正帆, 吉川 雄朗, 石塚 洋一, 近藤 悠希, 高橋 富美, 藤田 朋恵, 有賀 純, 近藤 一直, 岡田 尚志郎, 竹内 弘, 岡村 信行, 谷内 一彦
薬学教育, 5, 別刷, 97, 102, 日本薬学教育学会, 2021
Japanese

Chronic brain histamine depletion in adult mice induced depression-like behaviours and impaired sleep-wake cycle.
Yo Yamada, Takeo Yoshikawa, Fumito Naganuma, Takako Kikkawa, Noriko Osumi, Kazuhiko Yanai
Neuropharmacology, 175, 108179, 108179, 15 Sep. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Histamine acts as a neurotransmitter to regulate various physiological processes. Brain histamine is synthesized from an essential amino acid histidine in a reaction catalysed by histidine decarboxylase (Hdc). Hdc-positive neurons exist mainly in the tuberomammillary nucleus (TMN) of the posterior hypothalamus and project their axons to the entire brain. Recent studies have reported that a chronic decrease in histamine levels in the adult human brain was observed in several neurological disorders. However, it is poorly understood whether lower histamine levels play a causative role in those disorders. In the present study, we induced chronic histamine deficiency in the brains of adult mice to allow direct interpretation of the relationship between an impaired histaminergic nervous system and the resultant phenotype. To induce chronic brain histamine deficiency starting in adulthood, adeno-associated virus expressing Cre recombinase was microinjected into the TMN of Hdc flox mice (cKO mice) at the age of 8 weeks. Immunohistochemical analysis showed expression of Cre recombinase in the TMN of cKO mice. The reduction of histamine contents with the decreased Hdc expression in cKO brain was also confirmed. Behavioural studies revealed that chronic histamine depletion in cKO mice induced depression-like behaviour, decreased locomotor activity in the home cage, and impaired aversive memory. Sleep analysis showed that cKO mice exhibited a decrease in wakefulness and increase in non-rapid eye movement sleep throughout the day. Taken together, this study clearly demonstrates that chronic histamine depletion in the adult mouse brain plays a causative role in brain dysfunction.

Heparan sulfate controls skeletal muscle differentiation and motor functions.
Mariko Yokoyama, Takuro Matsuzawa, Takeo Yoshikawa, Aki Nunomiya, Yu Yamaguchi, Kazuhiko Yanai
Biochimica et biophysica acta. General subjects, 1864, 12, 129707, 129707, 15 Aug. 2020, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, BACKGROUND: Heparan sulfate (HS) is a sulfated linear polysaccharide on cell surfaces that plays an important role in physiological processes. HS is present in skeletal muscles but its detailed role in this tissue remains unclear. METHODS: We examined the role of HS in the differentiation of C2C12 cells, a mouse myoblast cell line. We also phenotyped the impact of HS deletion in mouse skeletal muscles on their functions by using Cre-loxP system. RESULTS: CRISPR-Cas9-dependent HS deletion or pharmacological removal of HS dramatically impaired myoblast differentiation of C2C12 cells. To confirm the importance of HS in vivo, we deleted Ext1, which encodes an enzyme essential for HS biosynthesis, specifically in the mouse skeletal muscles (referred to as mExt1CKO mice). Treadmill and wire hang tests demonstrated that mExt1CKO mice exhibited muscle weakness. The contraction of isolated soleus muscles from mExt1CKO mice was also impaired. Morphological examination of mExt1CKO muscle tissue under light and electron microscopes revealed smaller cross sectional areas and thinner myofibrils. Finally, a model of muscle regeneration following BaCl2 injection into the tibialis anterior muscle of mice demonstrated that mExt1CKO mice had reduced expression of myosin heavy chain and an increased number of centronucleated cells. This indicates that muscle regeneration after injury was attenuated in the absence of HS expression in muscle cells. SIGNIFICANCE: These results demonstrate that HS plays an important role in skeletal muscle function by promoting differentiation.

Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour.
Kárpáti A, Yoshikawa T, Naganuma F, Matsuzawa T, Kitano H, Yamada Y, Yokoyama M, Futatsugi A, Mikoshiba K, Yanai K
Scientific Reports, 9, 1, 16451, 16451, Nov. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Histamine is an important neurotransmitter that contributes to various processes, including the sleep-wake cycle, learning, memory, and stress responses. Its actions are mediated through histamine H1-H4 receptors. Gene knockout and pharmacological studies have revealed the importance of H1 receptors in learning and memory, regulation of aggression, and wakefulness. H1 receptors are abundantly expressed on neurons and astrocytes. However, to date, studies selectively investigating the roles of neuronal and astrocytic H1 receptors in behaviour are lacking. We generated novel astrocyte- and neuron-specific conditional knockout (cKO) mice to address this gap in knowledge. cKO mice showed cell-specific reduction of H1 receptor gene expression. Behavioural assessment revealed significant changes and highlighted the importance of H1 receptors on both astrocytes and neurons. H1 receptors on both cell types played a significant role in anxiety. Astrocytic H1 receptors were involved in regulating aggressive behaviour, circadian rhythms, and quality of wakefulness, but not sleep behaviour. Our results emphasise the roles of neuronal H1 receptors in recognition memory. In conclusion, this study highlights the novel roles of H1 receptors on astrocytes and neurons in various brain functions.

Brain histamine H1 receptor occupancy after oral administration of desloratadine and loratadine.
Tadaho Nakamura, Kotaro Hiraoka, Ryuichi Harada, Takuro Matsuzawa, Yoichi Ishikawa, Yoshihito Funaki, Takeo Yoshikawa, Manabu Tashiro, Kazuhiko Yanai, Nobuyuki Okamura
Pharmacology research & perspectives, 7, 4, e00499, Aug. 2019, [Peer-reviewed], [International Magazine]
English, Some histamine H1 receptor (H1R) antagonists induce adverse sedative reactions caused by blockade of histamine transmission in the brain. Desloratadine is a second-generation antihistamine for treatment of allergic disorders. Its binding to brain H1Rs, which is the basis of sedative property of antihistamines, has not been examined previously in the human brain by positron emission tomography (PET). We examined brain H1R binding potential ratio (BPR), H1R occupancy (H1RO), and subjective sleepiness after oral desloratadine administration in comparison to loratadine. Eight healthy male volunteers underwent PET imaging with [11C]-doxepin, a PET tracer for H1Rs, after a single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPR and H1RO in the cerebral cortex were calculated, and plasma concentrations of loratadine and desloratadine were measured. Subjective sleepiness was quantified by the Line Analogue Rating Scale (LARS) and the Stanford Sleepiness Scale (SSS). BPR was significantly lower after loratadine administration than after placebo (0.504 ± 0.074 vs 0.584 ± 0.059 [mean ± SD], P < 0.05), but BPR after desloratadine administration was not significantly different from BPR after placebo (0.546 ± 0.084 vs 0.584 ± 0.059, P = 0.250). The plasma concentration of loratadine was negatively correlated with BPR in subjects receiving loratadine, but that of desloratadine was not correlated with BPR. Brain H1ROs after desloratadine and loratadine administration were 6.47 ± 10.5% and 13.8 ± 7.00%, respectively (P = 0.103). Subjective sleepiness did not significantly differ among subjects receiving the two antihistamines and placebo. At therapeutic doses, desloratadine did not bind significantly to brain H1Rs and did not induce any significant sedation.

Site-Specific Labeling of F-18 Proteins Using a Supplemented Cell-Free Protein Synthesis System and O-2-[¹⁸F]Fluoroethyl-L-Tyrosine: [¹⁸F]FET-HER2 Affibody Molecule.
Yanai A, Harada R, Iwata R, Yoshikawa T, Ishikawa Y, Furumoto S, Ishida T, Yanai K
Molecular imaging and biology, 21, 3, 529, 537, Jun. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, PURPOSE: Although a preparation method for F-18-labeled proteins that used a cell-free translation system and 4-[18F]fluoro-L-proline instead of L-proline has been reported, its introduction depends on amino acid sequences of target proteins. The purpose of the study was to propose site-specific labeling method of F-18 by using cell-free translation systems supplemented with an engineered orthogonal aminoacyl-tRNA synthetase derived from Methanocaldococcus jannaschii (pCNF-RS)/suppressor tRNA (tRNACUAopt) pair, O-2-[18F]fluoroethyl-L-tyrosine ([18F]FET), and template DNA inserted with an amber codon. PROCEDURES: [18F]FET was prepared from the corresponding precursor and determined whether [18F]FET could be incorporated into an affibody molecule for human epidermal growth factor receptor type 2 (HER2; ZHER2:342) as the 21st amino acid used with the pCNF-RS-tRNACUAopt pair and template DNA inserted with an amber codon in a cell-free translation system. Using SKOV-3 cells, we performed an in vitro binding assay of [18F]FET-ZHER2:342. Furthermore, in vivo positron emission tomography (PET) imaging in SKOV-3 xenograft-bearing mice was performed after the intravenous administration of [18F]FET-ZHER2:342. RESULTS: [18F]FET was successfully incorporated into proteins by using commercially available cell-free protein synthesis reagents with a pCNF-RS-tRNACUAopt pair and template DNA of the desired proteins inserted with an amber codon. The mean radiochemical yield (non-decay-corrected) of [18F]FET-ZHER2:342 was 6.5 ± 4.1 %. An in vitro cell binding assay revealed that SKOV-3 cells-bound [18F]FET-ZHER2:342 expressed HER2. The in vivo PET imaging in SKOV-3 xenograft-bearing mice revealed that [18F]FET-ZHER2:342 accumulated in SKOV-3 xenografts. CONCLUSION: The method proposed in this study might be useful for preparing proteins with F-18 and molecular imaging in the preclinical development.

Histamine N-Methyltransferase in the Brain.
Yoshikawa T, Nakamura T, Yanai K
International journal of molecular sciences, 20, 3, 737, 737, MDPI AG, Feb. 2019, [Peer-reviewed], [Lead author, Corresponding author]
Scientific journal, Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood–brain barrier permeability have not been available until now. Recently, we have phenotyped Hnmt-deficient mice to elucidate the importance of HNMT in the central nervous system. Hnmt disruption resulted in a robust increase in brain histamine concentration, demonstrating the essential role of HNMT in the brain histamine system. Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson’s disease and attention deficit hyperactivity disorder. Postmortem studies also have indicated that HNMT expression is altered in human brain diseases. These findings emphasise that an increase in brain histamine levels by novel HNMT inhibitors could contribute to the improvement of brain disorders.

Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity
Ichinose, W., Sawato, T., Kitano, H., Shinozaki, Y., Arisawa, M., Saito, N., Yoshikawa, T., Yamaguchi, M.
Journal of Antibiotics, 72, 6, 2019, [Peer-reviewed]
Scientific journal

Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia - Crucial roles of endothelial nitric oxide synthase
Kumiko Eguchi, Tomohiko Shindo, Kenta Ito, Tsuyoshi Ogata, Ryo Kurosawa, Yuta Kagaya, Yuto Monma, Sadamitsu Ichijo, Sachie Kasukabe, Satoshi Miyata, Takeo Yoshikawa, Kazuhiko Yanai, Hirofumi Taki, Hiroshi Kanai, Noriko Osumi, Hiroaki Shimokawa
Brain Stimulation, 11, 5, 959, 973, Sep. 2018, [Peer-reviewed]
Scientific journal

【遺伝子改変マウスを用いた新しい創薬・薬理学研究の展開】新規遺伝子ノックアウトマウスを用いた脳内ヒスタミンクリアランス系の解明
吉川 雄朗, 中村 正帆, 谷内 一彦
日本薬理学雑誌, 152, 1, 16, 20, (公社)日本薬理学会, Jul. 2018
Japanese

Heparan sulfate in pancreatic β-cells contributes to normal glucose homeostasis by regulating insulin secretion
Takuro Matsuzawa, Takeo Yoshikawa, Tomomitsu Iida, Anikó Kárpáti, Haruna Kitano, Ryuichi Harada, Tadaho Nakamura, Akira Sugawara, Yu Yamaguchi, Kazuhiko Yanai
Biochemical and Biophysical Research Communications, 499, 3, 688, 695, Elsevier B.V., 15 May 2018, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Correlations of 18F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease.
Ryuichi Harada, Aiko Ishiki, Hideaki Kai, Naomi Sato, Katsutoshi Furukawa, Shozo Furumoto, Tetsuro Tago, Naoki Tomita, Shoichi Watanuki, Kotaro Hiraoka, Yoichi Ishikawa, Yoshihito Funaki, Tadaho Nakamura, Takeo Yoshikawa, Ren Iwata, Manabu Tashiro, Hironobu Sasano, Tetsuyuki Kitamoto, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo, Nobuyuki Okamura
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 59, 4, 671, 674, Apr. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Clinical PET studies using 18F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. Methods: We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed AD patient who underwent 18F-THK5351 and 11C-Pittsburgh compound B PET before death. Results: Regional in vivo 18F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. Conclusion:18F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain.

Histamine elicits glutamate release from cultured astrocytes
Anikó Kárpáti, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Takuro Matsuzawa, Haruna Kitano, Ryuichi Harada, Kazuhiko Yanai
Journal of Pharmacological Sciences, 137, 2, 122, 128, Japanese Pharmacological Society, 2018, [Peer-reviewed], [Corresponding author]
English, Scientific journal

[Analysis of brain histamine clearance using genetically engineered mice].
Yoshikawa T, Nakamura T, Yanai K
Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 152, 1, 16, 20, Japanese Pharmacological Society, 2018, [Peer-reviewed]
Scientific journal

The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion
Satoshi Aoki, Akiko Saito-Hakoda, Takeo Yoshikawa, Kyoko Shimizu, Kiyomi Kisu, Susumu Suzuki, Kiyoshi Takagi, Shuji Mizumoto, Shuhei Yamada, Toin H. Van Kuppevelt, Atsushi Yokoyama, Taiji Matsusaka, Hiroshi Sato, Sadayoshi Ito, Akira Sugawara
Nephrology Dialysis Transplantation, 33, 1, 26, 33, Oxford University Press, 01 Jan. 2018, [Peer-reviewed]
English, Scientific journal

Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice.
Shin-Ichi Inoue, Shingo Takahara, Takeo Yoshikawa, Tetsuya Niihori, Kazuhiko Yanai, Yoichi Matsubara, Yoko Aoki
Human molecular genetics, 26, 23, 4715, 4727, 01 Dec. 2017, [Peer-reviewed], [International Magazine]
English, Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome.

Histamine N-methyltransferase regulates aggression and the sleep-wake cycle
Fumito Naganuma, Tadaho Nakamura, Takeo Yoshikawa, Tomomitsu Iida, Yamato Miura, Aniko Karpati, Takuro Matsuzawa, Atushi Yanai, Asuka Mogi, Takatoshi Mochizuki, Nobuyuki Okamura, Kazuhiko Yanai
SCIENTIFIC REPORTS, 7, 1, 15899, Nov. 2017, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Induced histamine regulates Ni elution from an implanted Ni wire in mice by downregulating neutrophil migration
Yu Kishimoto, Sanki Asakawa, Taiki Sato, Takayuki Takano, Takahisa Nakajyo, Natsumi Mizuno, Ryosuke Segawa, Takeo Yoshikawa, Masahiro Hiratsuka, Kazuhiko Yanai, Hiroshi Ohtsu, Noriyasu Hirasawa
EXPERIMENTAL DERMATOLOGY, 26, 10, 868, 874, Oct. 2017, [Peer-reviewed]
English, Scientific journal

The clinical pharmacology of non-sedating antihistamines
Kazuhiko Yanai, Takeo Yoshikawa, Ai Yanai, Tadaho Nakamura, Tomomitsu Iida, Rob Leurs, Manabu Tashiro
PHARMACOLOGY & THERAPEUTICS, 178, 148, 156, Oct. 2017, [Peer-reviewed], [Corresponding author]
English, Scientific journal

JNJ10181457, a histamine H3 receptor inverse agonist, regulates in vivo microglial functions and improves depression-like behaviours in mice
Tomomitsu Iida, Takeo Yoshikawa, Aniko Karpati, Takuro Matsuzawa, Haruna Kitano, Asuka Mogi, Ryuichi Harada, Fumito Naganuma, Tadaho Nakamura, Kazuhiko Yanai
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 488, 3, 534, 540, Jul. 2017, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Characterization of murine polyspecific monoamine transporters
Yamato Miura, Takeo Yoshikawa, Fumito Naganuma, Tadaho Nakamura, Tomomitsu Iida, Aniko Karpati, Takuro Matsuzawa, Asuka Mogi, Ryuichi Harada, Kazuhiko Yanai
FEBS OPEN BIO, 7, 2, 237, 248, Feb. 2017, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Histamine clearance through polyspecific transporters in the brain
Yoshikawa, T., Yanai, K.
Handbook of Experimental Pharmacology, 241, 173, 187, 2017, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Synthesis and Characterization of F-18-Interleukin-8 Using a Cell-Free Translation System and 4-F-18-Fluoro-L-Proline
Ryuichi Harada, Shozo Furumoto, Takeo Yoshikawa, Yoichi Ishikawa, Katsuhiko Shibuya, Nobuyuki Okamura, Kiichi Ishiwata, Ren Iwata, Kazuhiko Yanai
JOURNAL OF NUCLEAR MEDICINE, 57, 4, 634, 639, Apr. 2016, [Peer-reviewed]
English, Scientific journal

F-18-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Katsutoshi Furukawa, Aiko Ishiki, Naoki Tomita, Tetsuro Tago, Kotaro Hiraoka, Shoichi Watanuki, Miho Shidahara, Masayasu Miyake, Yoichi Ishikawa, Rin Matsuda, Akie Inami, Takeo Yoshikawa, Yoshihito Funaki, Ren Iwata, Manabu Tashiro, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo
JOURNAL OF NUCLEAR MEDICINE, 57, 2, 208, 214, Feb. 2016, [Peer-reviewed]
English, Scientific journal

Histamine H1 Receptor Occupancy in the Human Brain Measured by Positron Emission Tomography
Kazuhiko Yanai, Kotaro Hiraoka, Anikó Kárpáti, Fumito Naganuma, Nobuyuki Okamura, Manabu Tashiro, Tadaho Nakamura, Takeo Yoshikawa
Histamine Receptors, 311, 325, Springer International Publishing, 2016
In book

Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression
Akiko Saito-Hakoda, Akira Uruno, Atsushi Yokoyama, Kyoko Shimizu, Rehana Parvin, Masataka Kudo, Takako Saito-Ito, Ikuko Sato, Naotaka Kogure, Dai Suzuki, Hiroki Shimada, Takeo Yoshikawa, Ikuma Fujiwara, Hiroyuki Kagechika, Yasumasa Iwasaki, Shigeo Kure, Sadayoshi Ito, Akira Sugawara
PLOS ONE, 10, 12, e0141960, Dec. 2015, [Peer-reviewed]
English, Scientific journal

Histamine H-1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers
Hirotoshi Sato, Chihiro Ito, Kotaro Hiraoka, Manabu Tashiro, Katsuhiko Shibuya, Yoshihito Funaki, Takeo Yoshikawa, Ren Iwata, Hiroo Matsuoka, Kazuhiko Yanai
PSYCHOPHARMACOLOGY, 232, 19, 3497, 3505, Oct. 2015, [Peer-reviewed]
English, Scientific journal

Histamine H-3 Receptor in Primary Mouse Microglia Inhibits Chemotaxis, Phagocytosis, and Cytokine Secretion
Tomomitsu Iida, Takeo Yoshikawa, Takuro Matsuzawa, Fumito Naganuma, Tadaho Nakamura, Yamato Miura, Attayeb S. Mohsen, Ryuichi Harada, Ren Iwata, Kazuhiko Yanai
GLIA, 63, 7, 1213, 1225, Jul. 2015, [Peer-reviewed], [Corresponding author]
English, Scientific journal

[F-18]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Katsutoshi Furukawa, Aiko Ishiki, Naoki Tomita, Kotaro Hiraoka, Shoichi Watanuki, Miho Shidahara, Masayasu Miyake, Yoichi Ishikawa, Rin Matsuda, Akie Inami, Takeo Yoshikawa, Tetsuro Tago, Yoshihito Funaki, Ren Iwata, Manabu Tashiro, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 42, 7, 1052, 1061, Jun. 2015, [Peer-reviewed]
English, Scientific journal

G-cell hyperplasia of the stomach induces ECL-cell proliferation in the pyloric glands in a paracrinal manner
Atsuko Kasajima, Fumiyoshi Fujishima, Takanori Morikawa, Shuhei Kawasaki, Sachiko Konosu-Fukaya, Yukiko Shibahara, Tadaho Nakamura, Takeo Yoshikawa, Katsunori Iijima, Tomoyuki Koike, Mika Watanabe, Chikashi Shibata, Hironobu Sasano
PATHOLOGY INTERNATIONAL, 65, 5, 259, 263, May 2015, [Peer-reviewed]
English, Scientific journal

Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity
Manabu Murakami, Takeo Yoshikawa, Tadaho Nakamura, Takayoshi Ohba, Yasushi Matsuzaki, Daisuke Sawamura, Kenji Kuwasako, Teruyuki Yanagisawa, Kyouichi Ono, Shigeyuki Nakaji, Kazuhiko Yanai
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 458, 3, 584, 589, Mar. 2015, [Peer-reviewed]
English, Scientific journal

Role of histamine H-3 receptor in glucagon-secreting alpha TC1.6 cells
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Attayeb Mohsen, Tomomitsu Iida, Yamato Miura, Akira Sugawara, Kazuhiko Yanai
FEBS OPEN BIO, 5, 36, 41, 2015, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Structural abnormality of the hippocampus associated with depressive symptoms in heart failure rats
Hideaki Suzuki, Akira Sumiyoshi, Yasuharu Matsumoto, Ben A. Duffy, Takeo Yoshikawa, Mark F. Lythgoe, Kazuhiko Yanai, Yasuyuki Taki, Ryuta Kawashima, Hiroaki Shimokawa
NEUROIMAGE, 105, 84, 92, Jan. 2015, [Peer-reviewed]
English, Scientific journal

Insufficient Intake of L-Histidine Reduces Brain Histamine and Causes Anxiety-Like Behaviors in Male Mice
Takeo Yoshikawa, Tadaho Nakamura, Tetsuro Shibakusa, Mayu Sugita, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Attayeb Mohsen, Ryuichi Harada, Kazuhiko Yanai
JOURNAL OF NUTRITION, 144, 10, 1637, 1641, Oct. 2014, [Peer-reviewed], [Lead author]
English, Scientific journal

Generation of a Stable H295R Cell Line Expressing 11beta-Hydroxylase Gene Promoter and the Effect of High-Glucose on Its Expression
Sugawara Kaori, Matsuda Ken, Kogure Naotaka, Uruno Akira, Sato Ikuko, Shimizu Kyoko, Parvin Rehana, Yoshikawa Takeo, Kudo Masataka, Saito-Hakoda Akiko, Ito Ryo, Yokoyama Atsushi, Ito Sadayoshi, Sugawara Akira
ENDOCRINE REVIEWS, 35, 3, Jun. 2014, [Peer-reviewed]

Mechanism of the histamine H-3 receptor-mediated increase in exploratory locomotor activity and anxiety-like behaviours in mice
Attayeb Mohsen, Takeo Yoshikawa, Yamato Miura, Tadaho Nakamura, Fumito Naganuma, Katsuhiko Shibuya, Tomomitsu Iida, Ryuichi Harada, Nobuyuki Okamura, Takehiko Watanabe, Kazuhiko Yanai
NEUROPHARMACOLOGY, 81, 188, 194, Jun. 2014, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Ryuichi Harada, Attayeb S. Mohsen, Yamato Miura, Kazuhiko Yanai
JOURNAL OF NEUROCHEMISTRY, 129, 4, 591, 601, May 2014, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells
Ken Matsuda, Akira Uruno, Naotaka Kogure, Kaori Sugawara, Hiroki Shimada, Masahiro Nezu, Takako Saito-Ito, Yuko Iki, Masataka Kudo, Kyoko Shimizu, Ikuko Sato, Takeo Yoshikawa, Fumitoshi Satoh, Ryo Ito, Atsushi Yokoyama, William E. Rainey, Akiko Saito-Hakoda, Sadayoshi Ito, Akira Sugawara
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 383, 1-2, 60, 68, Mar. 2014, [Peer-reviewed]
English, Scientific journal

Use of a Benzimidazole Derivative BF-188 in Fluorescence Multispectral Imaging for Selective Visualization of Tau Protein Fibrils in the Alzheimer's Disease Brain
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo
MOLECULAR IMAGING AND BIOLOGY, 16, 1, 19, 27, Feb. 2014, [Peer-reviewed]
English, Scientific journal

Coffee treatment prevents the progression of sarcopenia in aged mice in vivo and in vitro
Yinting Guo, Kaijun Niu, Tatsuma Okazaki, Hongmei Wu, Takeo Yoshikawa, Takashi Ohrui, Katsutoshi Furukawa, Masakazu Ichinose, Kazuhiko Yanai, Hiroyuki Arai, Guowei Huang, Ryoichi Nagatomi
EXPERIMENTAL GERONTOLOGY, 50, 1, 8, Feb. 2014, [Peer-reviewed]
English, Scientific journal

ARB affects nicotine-induced gene expression profile in human coronary artery endothelial cells　　　　　　　　　　　　　　　
Kudo M, Matsuda K, Sugawara K, Iki Y, Kogure N, Saito-Ito T, Shimizu K, Sato I, Yoshikawa T, Uruno A, Ito R, Yokoyama A, Saito-Hakoda A, Ito S, Sugawara A
World J Hypertens, 4, 1, 7, 14, 2014, [Peer-reviewed]
English

The expression and function of histamine H-3 receptors in pancreatic beta cells
T. Nakamura, T. Yoshikawa, N. Noguchi, A. Sugawara, A. Kasajima, H. Sasano, K. Yanai
BRITISH JOURNAL OF PHARMACOLOGY, 171, 1, 171, 185, Jan. 2014, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Is Heparan Sulfate in the Glomerular Basement Membrane Necessary for the Etiology of Diabetic Nephropathy?　　　　　　　　　　　　　　　
Akiko Saito-Hakoda, Naotaka Kogure, Takeo Yoshikawa, Kyoko Shimizu, Yuko Iki, Ikuko Sato, Masataka Kudo, Akira Uruno, Ken Matsuda, Rehana Parvin, Kaori Sugawara, Atushi Yokoyama, Sadayoshi Ito, Akira Sugawara
J Biomol Res Ther, 3, 2, 1000e127, Jan. 2014, [Peer-reviewed]
English, Scientific journal

Retinoic acid receptor-α up-regulates proopiomelanocortin gene expression in AtT20 corticotroph cells
Akira Uruno, Akiko Saito-Hakoda, Atsushi Yokoyama, Naotaka Kogure, Ken Matsuda, Rehana Parvin, Kyoko Shimizu, Ikuko Sato, Masataka Kudo, Takeo Yoshikawa, Hiroyuki Kagechika, Yasumasa Iwasaki, Sadayoshi Ito, Akira Sugawara
Endocrine Journal, 61, 11, 1105, 1114, Japan Endocrine Society, 2014, [Peer-reviewed]
English, Scientific journal

Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease.
Nobuyuki Okamura, Shozo Furumoto, Ryuichi Harada, Tetsuro Tago, Takeo Yoshikawa, Michelle Fodero-Tavoletti, Rachel S Mulligan, Victor L Villemagne, Hiroyasu Akatsu, Takayuki Yamamoto, Hiroyuki Arai, Ren Iwata, Kazuhiko Yanai, Yukitsuka Kudo
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 54, 8, 1420, 7, Aug. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal, UNLABELLED: Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the microtubule-associated protein tau. Noninvasive monitoring of tau protein aggregates in the living brain will provide useful information regarding tau pathophysiology in AD. However, no PET probes are currently available for selective detection of tau pathology in AD. We have previously reported (18)F-labeled THK-523 ((18)F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a tau imaging radiotracer candidate for PET. After compound optimization, we developed novel (18)F-labeled arylquinoline derivatives, (18)F-THK-5105 and (18)F-THK-5117, for use as tau imaging PET tracers. METHODS: (18)F-labeled compounds were prepared from the corresponding tosylated precursors. The binding affinity of compounds to synthetic tau aggregates and tau-rich AD brain homogenates was determined by saturation and competition binding assays. The binding selectivity of compounds to tau pathology was evaluated by autoradiography of AD brain sections. The pharmacokinetics of compounds were assessed in biodistribution studies in normal mice. A 14-d toxicity study with intravenous administration of compounds was performed using rats and mice. RESULTS: In vitro binding assays demonstrated higher binding affinity of THK-5105 and THK-5117 than THK-523 to tau protein aggregates and tau-rich AD brain homogenates. Autoradiographic analyses of AD brain sections showed that these radiotracers preferentially bound to neurofibrillary tangles and neuropil threads, which colocalized with Gallyas-positive and immunoreactive tau protein deposits. The distribution of this radiotracer binding in AD brain sections was completely different from that of (11)C-Pittsburgh compound B, showing preferential binding to amyloid plaques. Furthermore, these derivatives demonstrated abundant initial brain uptake and faster clearance in normal mice than (18)F-THK-523 and other reported (18)F-labeled radiotracers. THK-5105 and THK-5117 showed no toxic effects related to the administration of these compounds in mice and rats and no significant binding for various neuroreceptors, ion channels, and transporters at 1-μM concentrations. CONCLUSION: (18)F-labeled THK-5105 and THK-5117 are promising candidates as PET tau imaging radiotracers.

Molecular mechanism of histamine clearance by primary human astrocytes
Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Tadaho Nakamura, Ryuichi Harada, Attayeb S. Mohsen, Atsuko Kasajima, Hironobu Sasano, Kazuhiko Yanai
GLIA, 61, 6, 905, 916, Jun. 2013, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

高血糖刺激は副腎アルドステロン合成酵素の発現をT型Caチャネルの発現増加を介して誘導する
小暮 直敬, 伊藤 貴子, 菅原 香織, 松田 謙, 壹岐 裕子, 佐藤 郁子, 皆川 敬治, 勝木 将人, 清水 恭子, 吉川 雄朗, 工藤 正孝, 宇留野 晃, 箱田 明子, 伊藤 貞嘉, 菅原 明
日本内分泌学会雑誌, 89, 1, 278, 278, (一社)日本内分泌学会, Apr. 2013
Japanese

ニコチンのヒト冠動脈血管内皮細胞の遺伝子発現に及ぼす影響ならびにそれに対するARBの効果
壹岐 裕子, 工藤 正孝, 伊藤 貴子, 菅原 香織, 松田 謙, 小暮 直敬, 皆川 敬治, 勝木 将人, 佐藤 郁子, 宇留野 晃, 清水 恭子, 吉川 雄朗, 箱田 明子, 伊藤 貞嘉, 菅原 明
日本内分泌学会雑誌, 89, 1, 313, 313, (一社)日本内分泌学会, Apr. 2013
Japanese

Comparison of the binding characteristics of [F-18]THK-523 and other amyloid imaging tracers to Alzheimer's disease pathology
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Tetsuro Tago, Masahiro Maruyama, Makoto Higuchi, Takeo Yoshikawa, Hiroyuki Arai, Ren Iwata, Yukitsuka Kudo, Kazuhiko Yanai
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 40, 1, 125, 132, Jan. 2013, [Peer-reviewed]
English, Scientific journal

Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate
Takayuki Ikeda, Shin Takasawa, Naoya Noguchi, Koji Nata, Akiyo Yamauchi, Iwao Takahashi, Takeo Yoshikawa, Akira Sugawara, Hideto Yonekura, Hiroshi Okamoto
MOLECULAR AND CELLULAR BIOCHEMISTRY, 366, 1-2, 69, 80, Jul. 2012, [Peer-reviewed]
English, Scientific journal

[ 11C]doxepin binding to histamine H1 receptors in living human brain: Reproducibility during attentive waking and circadian rhythm
Katsuhiko Shibuya, Yoshihito Funaki, Kotaro Hiraoka, Takeo Yoshikawa, Fumito Naganuma, Masayasu Miyake, Shoichi Watanuki, Hirotoshi Sato, Manabu Tashiro, Kazuhiko Yanai
Frontiers in Systems Neuroscience, 6, 2012, 45, 45, 11 Jun. 2012, [Peer-reviewed]
English, Scientific journal

Synthesis of [C-11]interleukin 8 using a cell-free translation system and L-[C-11]methionine
Ryuichi Harada, Shozo Furumoto, Takeo Yoshikawa, Yoichi Ishikawa, Katsuhiko Shibuya, Nobuyuki Okamura, Ren Iwata, Kazuhiko Yanai
NUCLEAR MEDICINE AND BIOLOGY, 39, 1, 155, 160, Jan. 2012, [Peer-reviewed]
English, Scientific journal

All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-delta
Akira Uruno, Naoya Noguchi, Ken Matsuda, Koji Nata, Takeo Yoshikawa, Youichiro Chikamatsu, Hiroyuki Kagechika, Hideo Harigae, Sadayoshi Ito, Hiroshi Okamoto, Akira Sugawara
JOURNAL OF LEUKOCYTE BIOLOGY, 90, 2, 235, 247, Aug. 2011, [Peer-reviewed]
English, Scientific journal

Positron emission tomography evaluation of sedative properties of antihistamines
Kazuhiko Yanai, Dongying Zhang, Manabu Tashiro, Takeo Yoshikawa, Fumito Naganuma, Ryuichi Harada, Tadaho Nakamura, Katsuhiko Shibuya, Nobuyuki Okamura
EXPERT OPINION ON DRUG SAFETY, 10, 4, 613, 622, Jul. 2011, [Peer-reviewed]
English, Scientific journal

Peroxisome proliferator-activated receptor-gamma suppresses CYP11B2 expression and aldosterone production
Akira Uruno, Ken Matsuda, Naoya Noguchi, Takeo Yoshikawa, Masataka Kudo, Fumitoshi Satoh, William E. Rainey, Xiao-Gang Hui, Jun-ichi Akahira, Yasuhiro Nakamura, Hironobu Sasano, Hiroshi Okamoto, Sadayoshi Ito, Akira Sugawara
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 46, 1, 37, 49, Feb. 2011, [Peer-reviewed]
English, Scientific journal

In vivo Detection of Amyloid Plaques in the Mouse Brain using the Near-Infrared Fluorescence Probe THK-265
Nobuyuki Okamura, Masanori Mori, Shozo Furumoto, Takeo Yoshikawa, Ryuichi Harada, Satoshi Ito, Yosuke Fujikawa, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo
JOURNAL OF ALZHEIMERS DISEASE, 23, 1, 37, 48, 2011, [Peer-reviewed]
English, Scientific journal

Roles of Hypothalamic Subgroup Histamine and Orexin Neurons on Behavioral Responses to Sleep Deprivation Induced by the Treadmill Method in Adolescent Rats
Ajing Xu, Eilko Sakurai, Atsuo Kuramasu, Jian Zhang, Jiyu Li, Nobuyuki Okamura, Dongying Zhang, Takeo Yoshikawa, Takehiko Watanabe, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 114, 4, 444, 453, Dec. 2010, [Peer-reviewed]
English, Scientific journal

Next-Day Residual Sedative Effect After Nighttime Administration of an Over-the-Counter Antihistamine Sleep Aid, Diphenhydramine, Measured by Positron Emission Tomography
Dongying Zhang, Manabu Tashiro, Katsuhiko Shibuya, Nobuyuki Okamura, Yoshihito Funaki, Takeo Yoshikawa, Masato Kato, Kazuhiko Yanai
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 30, 6, 694, 701, Dec. 2010, [Peer-reviewed]
English, Scientific journal

Upregulation of REG I alpha accelerates tumor progression in pancreatic cancer with diabetes
Lin Zhou, Ruifeng Zhang, Lishun Wang, Shaoming Shen, Hiroshi Okamoto, Akira Sugawara, Li Xia, Xiaoling Wang, Naoya Noguchi, Takeo Yoshikawa, Akira Uruno, Weiyan Yao, Yaozong Yuan
INTERNATIONAL JOURNAL OF CANCER, 127, 8, 1795, 1803, Oct. 2010, [Peer-reviewed]
English, Scientific journal

A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene
Shin Takasawa, Michio Kuroki, Koji Nata, Naoya Noguchi, Takayuki Ikeda, Akiyo Yamauchi, Hiroyo Ota, Asako Itaya-Hironaka, Sumiyo Sakuramoto-Tsuchida, Iwao Takahashi, Takeo Yoshikawa, Tooru Shimosegawa, Hiroshi Okamoto
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 397, 2, 140, 145, Jun. 2010, [Peer-reviewed]
English, Scientific journal

Methamphetamine- and 3,4-Methylenedioxymethamphetamine-Induced Behavioral Changes in Histamine H-3-Receptor Knockout Mice
Tomohiro Okuda, Dongying Zhang, He Shao, Nobuyuki Okamura, Naoko Takino, Tatsunori Iwamura, Eiko Sakurai, Takeo Yoshikawa, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 111, 2, 167, 174, Oct. 2009, [Peer-reviewed]
English, Scientific journal

FKBP12.6ノックアウトマウスではブドウ糖刺激インスリン分泌が低下する
吉川雄朗
東北医学雑誌, 121, 1, 84, 87, Jun. 2009, [Invited]
Japanese, Scientific journal

Important role of heparan sulfate in postnatal islet growth and insulin secretion
Iwao Takahashi, Naoya Noguchi, Koji Nata, Shuhei Yamada, Tomoyuki Kaneiwa, Shuji Mizumoto, Takayuki Ikeda, Kazushi Sugihara, Masahide Asano, Takeo Yoshikawa, Akiyo Yamauchi, Nausheen Jamal Shervani, Akira Uruno, Ichiro Kato, Michiaki Unno, Kazuyuki Sugahara, Shin Takasawa, Hiroshi Okamoto, Akira Sugawara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 383, 1, 113, 118, May 2009, [Peer-reviewed]
English, Scientific journal

Thiazolidinediones inhibit REG I alpha gene transcription in gastrointestinal cancer cells
Akiyo Yamauchi, Iwao Takahashi, Shin Takasawa, Koji Nata, Naoya Noguchi, Takayuki Ikeda, Takeo Yoshikawa, Nausheen J. Shervani, Iwao Suzuki, Akira Uruno, Michiaki Unno, Hiroshi Okamoto, Akira Sugawara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 379, 3, 743, 748, Feb. 2009, [Peer-reviewed]
English, Scientific journal

FKBP12.6 disruption impairs glucose-induced insulin secretion
Naoya Noguchi, Takeo Yoshikawa, Takayuki Ikeda, Iwao Takahashi, Nausheen Jamal Shervani, Akira Uruno, Akiyo Yamauchi, Koji Nata, Shin Takasawa, Hiroshi Okamoto, Akira Sugawara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 371, 4, 735, 740, Jul. 2008, [Peer-reviewed], [Lead author]
English, Scientific journal

Genomic organization, chromosomal localization, and promoter of human gene for FK506-binding protein 12.6
T Nakazawa, S Takasawa, N Noguchi, K Nata, A Tohgo, M Mori, K Nakagawara, T Akiyama, T Ikeda, A Yamauchi, Takahashi, I, T Yoshikawa, H Okamoto
GENE, 360, 1, 55, 64, Oct. 2005, [Peer-reviewed]
English, Scientific journal

An Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity against Breast Cancer in Mouse Xenograft Model
Takeo Yoshikawa

ヒスタミン代謝酵素阻害薬の薬理作用について
吉川雄朗, GIRGIN Birkan, AGU Anne Bernadette, 谷内一彦, 中村正帆, 長沼史登, 日本ヒスタミン学会プログラム・講演要旨集, 24th, 2024

ヒスタミン代謝酵素阻害剤メトプリンの行動薬理学的検討
吉川雄朗, 長沼史登, 長沼史登, 長谷茜音, 谷内一彦, 中村正帆, 中村正帆, 日本薬理学雑誌, 158, Supplement, 2023

ヒスタミン代謝酵素阻害薬のナルコレプシー治療に対する有用性の検討
長沼史登, 長沼史登, GIRGIN Birkan, BERNADETTE S Agu Anne, 中村正帆, 谷内一彦, 吉川雄朗, 吉川雄朗, 時間生物学, 29, 2, 2023

扁桃体中心核ニューロテンシン神経細胞の睡眠覚醒サイクルにおける役割の検討
中村 正帆, 長沼 史登, 田中 聖人, 井上 まり絵, 直野 留美, 吉川 雄朗, 岡村 信行, 応用薬理, 102, 5-6, 128, 128, Aug. 2022
応用薬理研究会, Japanese

ブドウ糖代謝におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
吉川 雄朗, 松澤 拓郎, 谷内 一彦, 山口 祐, 糖尿病, 65, Suppl.1, S, 282, Apr. 2022
(一社)日本糖尿病学会, Japanese

【皮膚科医が学ぶ睡眠医学-皮膚科診療に活かそう!】(Part1.)皮膚科医が知っておくべき睡眠の科学(総説7) ヒスタミンH1受容体拮抗薬による眠気と鎮静作用発生メカニズム　　　　　　　　　　　　　　　
谷内 一彦, 吉川 雄朗, Visual Dermatology, 21, 3, 262, 265, Feb. 2022
(株)学研メディカル秀潤社, Japanese

神経細胞に発現するヒスタミン代謝酵素の重要性について
吉川雄朗, 長沼史登, 長沼史登, 長谷茜音, 長谷茜音, 谷内一彦, 中村正帆, 中村正帆, 日本生化学会大会(Web), 95th, 2022

Chronic histamine deletion in adult mouse brain induced depression-like behaviors, impairment of memory function and decrease of locomotor activity
吉川雄朗, 長沼史登, 長沼史登, 山田瑶, 吉川貴子, 大隅典子, 谷内一彦, 日本神経精神薬理学会プログラム・抄録集, 50th, 179, 179, 2020
日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会, Japanese

膵β細胞におけるグルコース応答性転写因子ChREBPの機能制御因子の探索　　　　　　　　　　　　　　　
横山 敦, 野呂 英理香, 松澤 拓郎, 吉川 雄朗, 島 弘季, 五十嵐 和彦, 菅原 明, 日本生化学会大会プログラム・講演要旨集, 92回, [3T15m, 04], Sep. 2019
(公社)日本生化学会, Japanese

Histamine H1 receptor occupancy measured by PET in the human brain after oral administration of desloratadine
Tadaho Nakamura, Takeo Yoshikawa, Manabu Tashiro, Nobuyuki Okamura, Kazuhiko Yanai, Inflammation Research, 68, S1, S14, S15, Jul. 2019
Springer Science and Business Media LLC, English, Summary international conference

無細胞蛋白合成系を用いたタンパク質の部位特異的フッ素18標識法　　　　　　　　　　　　　　　
谷内 一彦, 原田 龍一, 谷内 亜衣, 吉川 雄朗, 古本 祥三, 岩田 錬, JSMI Report, 12, 2, 97, 97, May 2019
日本分子イメージング学会, Japanese

白色脂肪細胞におけるヘパラン硫酸は糖の恒常性の維持に重要である　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 谷内 一彦, 糖尿病, 62, Suppl.1, S, 179, Apr. 2019
(一社)日本糖尿病学会, Japanese

Affibodyの新規18F標識法によるHER2、PD-L1発現腫瘍の分子イメージング　　　　　　　　　　　　　　　
谷内 亜衣, 原田 龍一, 岩田 錬, 吉川 雄朗, 古本 祥三, 谷内 一彦, 内藤 剛, 海野 倫明, 亀井 尚, 石田 孝宜, 日本外科学会定期学術集会抄録集, 119回, PS, 110, Apr. 2019
(一社)日本外科学会, Japanese

ヒスチジンの疲労感低減機能に関する研究　　　　　　　　　　　　　　　
笹原 育子, 安居 昌子, 杉田 麻友, 柴草 哲郎, 藤村 尚子, 野沢 与志津, 吉川 雄朗, 谷内 一彦, アミノ酸研究, 12, 1, 58, 58, Feb. 2019
日本アミノ酸学会, Japanese

Brain histamine H₁ receptor occupancy measured by PET after oral administration of desloratadine and loratadine
Nakamura Tadaho, Hiraoka Kotaro, Harada Ryuchi, Matsuzawa Takuro, Yoshikawa Takeo, Tashiro Manabu, Yanai Kazuhiko, Okamura Nobuyuki, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 92, 0, 3, O-25, 2019

Objective: Some histamine H₁ receptor (H₁R) antagonists have sedative effects, caused by the blockade of histamine neural transmission. Desloratadine is a newly-marked antihistamine, but its sedative properties have not been examined by positron emission tomography (PET). We examined the brain H₁R binding potential ratio (BPR), H₁R occupancy (H₁RO) and the subjective sleepiness after oral administration of desloratadine and loratadine, the prodrug of desloratadine.

Methods: Eight healthy male volunteers underwent PET imaging with [¹¹C]doxepin after single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPRs and H₁ROs in the cerebral cortices were calculated. Subjective sleepiness was quantified by the LARS and the SSS.

Results: BPR after loratadine administration was significantly lower than placebo (p<0.05), but BPR after desloratadine was not significant. There was no significant difference, however, between H₁RO after desloratadine and loratadine administration. The subjective sleepiness was not significantly different among the two antihistamines and placebo.

Conclusion: At therapeutic dose, desloratadine did not bind significantly to brain H₁Rs and did not cause significant sedation.

, Japanese Pharmacological Society, Japanese

脳内ヒスタミン除去機構を標的とした創薬研究 ヒスタミン代謝酵素HNMTの機能解明と阻害剤探索　　　　　　　　　　　　　　　
吉川 雄朗, 北野 陽菜, 谷内 一彦, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 28回・48回, 221, 221, Nov. 2018
日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese

【神経系のトランスポーター-Up to date】トランスポーターの基礎 モノアミントランスポーター　　　　　　　　　　　　　　　
吉川 雄朗, 北野 陽菜, 谷内 一彦, Clinical Neuroscience, 36, 6, 652, 655, Jun. 2018
(株)中外医学社, Japanese

Affibodyの新規18F標識法によるHER2発現乳癌の分子イメージング　　　　　　　　　　　　　　　
谷内 亜衣, 原田 龍一, 岩田 錬, 吉川 雄朗, 古本 祥三, 谷内 一彦, 石田 孝宣, 日本乳癌学会総会プログラム抄録集, 26回, 431, 431, May 2018
(一社)日本乳癌学会, Japanese

Affibodyの新規18F標識法によるHER2発現乳癌の分子イメージング　　　　　　　　　　　　　　　
谷内 亜衣, 原田 龍一, 岩田 錬, 吉川 雄朗, 古本 祥三, 谷内 一彦, 石田 孝宣, 日本乳癌学会総会プログラム抄録集, 26回, 431, 431, May 2018
(一社)日本乳癌学会, Japanese

脂肪組織におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 谷内 一彦, 糖尿病, 61, Suppl.1, S, 320, Apr. 2018
(一社)日本糖尿病学会, Japanese

がん原遺伝子Brafの活性化はマウス食道の拡張と前胃上皮の過増殖をもたらす　　　　　　　　　　　　　　　
井上 晋一, 高原 真吾, 吉川 雄朗, 新堀 哲也, 谷内 一彦, 松原 洋一, 青木 洋子, 生命科学系学会合同年次大会, 2017年度, [1LBA, 090], Dec. 2017
生命科学系学会合同年次大会運営事務局, Japanese

膵β細胞におけるヘパラン硫酸はインスリン分泌及び糖の恒常性維持に重要である　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 中村 正帆, 谷内 一彦, 生命科学系学会合同年次大会, 2017年度, [1AT26, 0059)], Dec. 2017
生命科学系学会合同年次大会運営事務局, Japanese

Low intensity Pulsed Ultrasound Ameliorates Cognitive Impairment in a Mouse Model of Vascular Dementia
Kumiko Eguchi, Kenta Ito, Tomohiko Shindo, Ryo Kurosawa, Yuta Kagaya, Yuto Monma, Sadamitsu Ichijyo, Satoshi Miyata, Takeo Yoshikawa, Kazuhiko Yanai, Hirofumi Taki, Hiroshi Kanai, Noriko Osumi, Hiroaki Shimokawa, CIRCULATION, 136, Nov. 2017
English, Summary international conference

ヒスタミン3型受容体インバースアゴニストによるミクログリア機能抑制について(Suppression of microglial functions by an H3R inverse agonist)　　　　　　　　　　　　　　　
飯田 智光, 吉川 雄朗, 谷内 一彦, 日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, 39回・47回, 202, 202, Sep. 2017
日本生物学的精神医学会・日本神経精神薬理学会, English

脳内ヒスタミン神経系の過剰な興奮はH2受容体を介してマウスの攻撃性を増加させる　　　　　　　　　　　　　　　
吉川 雄朗, 飯田 智光, 長沼 史登, 中村 正帆, 岡村 信行, 谷内 一彦, 日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, 39回・47回, 151, 151, Sep. 2017
日本生物学的精神医学会・日本神経精神薬理学会, Japanese

The effect of H3 receptor antagonism on rat neuropathic nociception
Tadaho Nakamura, Takuro Matsuzawa, Maria Mogilevskaya, Takeo Yoshikawa, Fumito Naganuma, Nobuyuki Okamura, Kazuhiko Yanai, Inflammation Research, 66, S1, S22, SS22, Jul. 2017
Springer Science and Business Media LLC, English, Summary international conference

Development of a lanthanide complex labeled beta-sheet ligand for high-throughput screening using time-resolved fluorescence method
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Yukitsuka Kudo, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 133, 3, S131, S131, Mar. 2017
English, Summary international conference

CHARACTERIZATION OF F-18-BF227 IN A MOUSE MODEL OF STEREOTAXIC alpha-SYNUCLEIN AGGREGATE INJECTIONS
Michael Elmer Jan Stouthandel, Ryuichi Harada, Yoshimi Hayakawa, Takeo Yoshikawa, Shozo Furumoto, Yukitsuka Kudo, Nobuyuki Okamura, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 133, 3, S236, S236, Mar. 2017
English, Summary international conference

Histamine induced gliotransmitter release from cortical rat astrocytes
Aniko Karpati, Takeo Yoshikawa, Tadaho Nakamura, Fumito Naganuma, Tomomitsu Iida, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 133, 3, S89, S89, Mar. 2017
English, Summary international conference

Role of histamine receptors in desflurane anesthesia
Toru Tamii, Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Aniko Karpati, Takuro Matsuzawa, Haruna Kitano, Nobuyuki Okamura, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 133, 3, S171, S171, Mar. 2017
English, Summary international conference

【蕁麻疹の原因と最新治療】 臨床薬理学からみた非鎮静性抗ヒスタミン薬　　　　　　　　　　　　　　　
谷内 一彦, 谷内 亜衣, 中村 正帆, 吉川 雄朗, アレルギーの臨床, 37, 1, 35, 39, Jan. 2017
(株)北隆館, Japanese

吸入麻酔薬の意識消失作用におけるヒスタミン受容体の役割
民井亨, 民井亨, 中村正帆, 吉川雄朗, 長沼史登, 飯田智光, KARPATI Aniko, 松澤拓郎, 北野陽菜, 山内正憲, 岡村信行, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 68th, 2017

骨格筋におけるヘパラン硫酸の重要性について　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 三浦 大和, 谷内 一彦, 日本生化学会大会プログラム・講演要旨集, 89回, [3P, 372], Sep. 2016
(公社)日本生化学会, Japanese

Electroencephalogram of H1KO mice under isoflurane anesthesia
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Aniko Karpati, Toru Tamii, Nobuyuki Okamura, Kazuhiko Yanai, Inflammation Research, 65, S1, S26, S26, Jul. 2016
Springer Science and Business Media LLC, English, Summary international conference

Role of brain histamine in glutamate release from cultured astrocytes
Aniko Karpati, Takeo Yoshikawa, Tadaho Nakamura, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 130, 3, S83, S83, Mar. 2016
English, Summary international conference

Histamine N-methyltransferase deficiency causes abnormal sleep-wake cycles and aggressive behaviors
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Ai Horigome, Yamato Miura, Atsushi Yanai, Takatoshi Mochizuki, Kazuhiku Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 130, 3, S112, S112, Mar. 2016
English, Summary international conference

Interactions between histaminergic neuronal system and isoflurane anesthesia in mice
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Aniko Karpati, Takatoshi Mochizuki, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 130, 3, S98, S98, Mar. 2016
English, Summary international conference

ニューロン新生マーカー・BrdUの脳内分布における拡散型ヌクレオシドトランスポーター1の役割の解明
木村隼也, 吉田寛伸, 竹生田淳, BASTOS Gilmara, 鈴木登紀子, 吉川雄朗, 根本亙, 中川西修, 丹野孝一, 谷内一彦, 平澤典保, 守屋孝洋, 日本薬理学会北部会プログラム・抄録集, 67th, 2016

ヒスタミンによるミクログリア機能制御について　　　　　　　　　　　　　　　
吉川 雄朗, 飯田 智光, 松澤 拓郎, 中村 正帆, 谷内 一彦, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1LBA126], [1LBA126], Dec. 2015
(公社)日本生化学会, Japanese

H1-knocked out mouse has high sensitivity to isoflurane-induced anesthesia
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Kazuhiko Yanai, Inflammation Research, 64, S1, S22, S22, Jul. 2015
Springer Science and Business Media LLC, English, Summary international conference

Analysis of skeletal muscle-specific Ext1 lacking mice
Yamato Miura, Takeo Yoshikawa, Tadaho Nakamura, Fumito Naganuma, Tomomitsu Iida, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128, 3, S94, S94, Jul. 2015
English, Summary international conference

Analysis of Histamine N-methyltransferase deficitent mice
Fumito Naganuma, Takeo Yoshikawa, Yamato Miura, Ayano Yagyuu, Tadaho Nakamura, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128, 3, S87, S87, Jul. 2015
English, Summary international conference

Role of neuronal histamine and histamine H-1 receptor in isoflurane anesthesia
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128, 3, S189, S189, Jul. 2015
English, Summary international conference

種々のレチノイドX受容体アゴニストは、AtT20細胞の増殖・アポトーシス・Pomc発現・ACTH分泌に異なる影響を及ぼす
箱田 明子, 宇留野 晃, 清水 恭子, パービン・レハナ, 横山 敦, 吉川 雄朗, 工藤 正孝, 影近 弘之, 岩崎 泰正, 伊藤 貞嘉, 菅原 明, 日本内分泌学会雑誌, 91, 1, 269, 269, Apr. 2015
(一社)日本内分泌学会, Japanese

ヒスタミン神経系におけるイソフルランの作用
中村正帆, 吉川雄朗, 長沼史登, 三浦大和, 飯田智光, 松澤拓郎, 堀米愛, KARPATI Aniko, 谷内一彦, 日本ヒスタミン学会プログラム・講演要旨集, 19th, 2015

生体内ミクログリアにおける中枢ヒスタミン系の役割
飯田智光, 吉川雄朗, 松澤拓郎, 長沼史登, 中村正帆, 三浦大和, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 66th, 2015

イソフルランの麻酔作用におけるヒスタミン神経系の役割
中村正帆, 吉川雄朗, 長沼史登, 三浦大和, 飯田智光, 松澤拓郎, 堀米愛, ANIKO Karpati, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 66th, 2015

Histamine N-methyltransferaseの欠損はマウスにおいて攻撃性を高め,睡眠サイクルの異常を引き起こす
長沼史登, 吉川雄朗, 堀米愛, 三浦大和, 中村正帆, 矢内敦, 矢内敦, 望月貴年, 谷内一彦, 日本神経精神薬理学会プログラム・抄録集, 45th, 2015

Histamine N-methyltransferaseの欠損はマウスにおいて睡眠覚醒サイクルの異常を引き起こす
長沼史登, 吉川雄朗, 中村正帆, 堀米愛, 三浦大和, 矢内敦, 矢内敦, 望月貴年, 谷内一彦, 矢内敦, 望月貴年, 日本ヒスタミン学会プログラム・講演要旨集, 19th, 2015

Development of 18F-labeling Method for Proteins Using a Cell-free Translation System and 18F-fluoro-L-proline
Harada R., Furumoto S., Yoshikawa T., Ishikawa Y., Iwata R., Yanai K., CYRIC annual report, 2014, 69, 72, 2015
Cyclotron and Radioisotope Center, Tohoku University, English

高血糖刺激による副腎アルドステロン合成酵素遺伝子(CYP11B2)発現亢進の分子機構　　　　　　　　　　　　　　　
小暮 直敬, 菅原 香織, 松田 謙, 宇留野 晃, 佐藤 郁子, 清水 恭子, レハナ・パービン, 島田 洋樹, 吉川 雄朗, 工藤 正孝, 箱田 明子, 伊藤 亮, 横山 敦, 伊藤 貞嘉, 菅原 明, 日本高血圧学会総会プログラム・抄録集, 37回, 333, 333, Oct. 2014
(NPO)日本高血圧学会, Japanese

高血糖刺激は副腎11β-水酸化酵素遺伝子(CYP11B1)の発現を誘導する　　　　　　　　　　　　　　　
菅原 香織, 小暮 直敬, 松田 謙, 宇留野 晃, 佐藤 郁子, 清水 恭子, レハナ・パービン, 島田 洋樹, 吉川 雄朗, 工藤 正孝, 箱田 明子, 伊藤 亮, 横山 敦, 伊藤 貞嘉, 菅原 明, 日本高血圧学会総会プログラム・抄録集, 37回, 399, 399, Oct. 2014
(NPO)日本高血圧学会, Japanese

Expression and function of histamine H3 receptor in pancreatic islets
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Ryuichi Harada, Attayb Mohsen, Kazuhiko Yanai, Basic & Clinical Pharmacology & Toxicology, 115, S241, S241, Jul. 2014
Wiley, English, Summary international conference

タウイメージングトレーサー18F-THK5117の結合メカニズムの検討　　　　　　　　　　　　　　　
原田 龍一, 岡村 信行, 古本 祥三, 多胡 哲郎, 吉川 雄朗, 荒井 啓行, 谷内 一彦, 工藤 幸司, JSMI Report, 7, 2, 108, 108, May 2014
日本分子イメージング学会, Japanese

ヒスタミン代謝酵素欠損マウスの解析
吉川雄朗, 長沼史登, 三浦大和, 柳生彩乃, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 65th, 2014

睡眠剥奪ストレスに惹起される不安様行動は、ヒスタミン摂取により低減される　　　　　　　　　　　　　　　
長沼 史登, Mohsen Attayeb, 吉川 雄朗, 谷内 一彦, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 23回・43回, 248, 248, Oct. 2013
日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese

ヒトアストロサイトーマ由来細胞株1321N1はPMATを介してモノアミンを取り込む　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 飯田 智光, 谷内 一彦, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 23回・43回, 193, 193, Oct. 2013
日本臨床精神神経薬理学会・日本神経精神薬理学会, English

タウイメージング用トレーサー[18F]THK-5117の前臨床評価　　　　　　　　　　　　　　　
原田 龍一, 岡村 信行, 古本 祥三, 多胡 哲郎, 吉川 雄朗, 荒井 啓行, 岩田 錬, 谷内 一彦, 工藤 幸司, Dementia Japan, 27, 4, 505, 505, Oct. 2013
(一社)日本認知症学会, Japanese

The role of histamine receptors on glucagon secretion in atc1.6 cell
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Ryuichi Harada, Attayb Mohsen, Kazuhiko Yanai, Inflammation Research, 62, S1, S40, S40, Jul. 2013
Springer Science and Business Media LLC, English, Summary international conference

Histamine transport by mouse plasma membrane monoamine transporter and mouse organic cation transporter 3
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Ryuichi Harada, Attayb Mohsen, Kazuhiko Yanai, Inflammation Research, 62, S1, S32, S32, Jul. 2013
Springer Science and Business Media LLC, English, Summary international conference

脳・心臓 タウイメージング用トレーサー[18F]THK-5117の結合性評価　　　　　　　　　　　　　　　
原田 龍一, 岡村 信行, 古本 祥三, 多胡 哲朗, 吉川 雄朗, 荒井 啓行, 谷内 一彦, 工藤 幸司, JSMI Report, 6, 2, 71, 71, May 2013
日本分子イメージング学会, Japanese

タウイメージング用トレーサー[18]THK-5117の結合性評価　　　　　　　　　　　　　　　
原田 龍一, 岡村 信行, 古本 祥三, 多胡 哲朗, 吉川 雄朗, 荒井 啓行, 谷内 一彦, 工藤 幸司, JSMI Report, 6, 2, 100, 100, May 2013
日本分子イメージング学会, Japanese

非鎮静性抗ヒスタミン薬の薬理学的特徴　　　　　　　　　　　　　　　
中村正帆, 長沼史登, 谷内一彦, 吉川雄朗, アレルギーの臨床, 33, 439, 22, 26, 20 Jan. 2013
Japanese, Introduction scientific journal

ヒトアストロサイトーマ由来細胞株1321N1細胞におけるセロトニン取り込み機構の解明　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 飯田 智光, 谷内 一彦, 日本薬理学雑誌, 141, 1, 2P, 2P, Jan. 2013
(公社)日本薬理学会, Japanese

小動物PET/CTを用いた抗ヒスタミン薬レボセチリジンの鎮静性評価　　　　　　　　　　　　　　　
飯田 智光, 船木 善仁, 石渡 喜一, 長沼 史登, 原田 龍一, 吉川 雄朗, 古本 祥三, 岩田 錬, 谷内 一彦, 日本薬理学雑誌, 141, 1, 3P, 3P, Jan. 2013
(公社)日本薬理学会, Japanese

Development of a novel near-infrared fluorescence probe X65 for in vivo detection of amyloid fibrils
Nobuyuki Okamura, Ryuichi Harada, Shozo Furumoto, Takeo Yoshikawa, Yukitsuka Kudo, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 220P, 220P, 2013
English, Summary international conference

低親和性モノアミントランスポーターの機能解析
三浦大和, 吉川雄朗, 長沼史登, 中村正帆, 飯田智光, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 64th, 2013

ヒスタミンはヒスタミンH3受容体を介してミクログリアの機能を抑制する
飯田智光, 飯田智光, 吉川雄朗, 根東明広, 長沼史登, 中村正帆, 三浦大和, 岩田錬, 谷内一彦, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 64th, 2013

抗ヒスタミン薬~新たな地平~1 ヒスタミンの生理作用:“善玉”としてのヒスタミン
飯田智光, 三浦大和, 長沼史登, 中村正帆, 吉川雄朗, 谷内一彦, 皮膚アレルギーフロンティア, 11, 2, 2013

アレルギー疾患と睡眠 6.ヒスタミンと睡眠との関わり:ヒスタミン神経系の覚醒と睡眠
三浦大和, 飯田智光, 長沼史登, 中村正帆, 吉川雄朗, 谷内一彦, Progress in Medicine, 33, 12, 2013

Histamine stimulated phagocytosis of the primary rat microglia
Tomomitsu Iida, Takeo Yoshikawa, Akihiro Kondo, Tadaho Nakamura, Fumito Naganuma, Ryuichi Harada, Ren Iwata, Kazuhiko Yanai, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 217P, 217P, 2013
English, Summary international conference

Comparison of the Binding Properties of Tau PET Radiotracer 18F-THK523 and Other Amyloid PET Tracers to Alzheimer's Disease Pathology
Harada R., Okamura N., Furumoto S., Tago T., Yoshikawa T., Arai H., Iwata R., Yanai K., Kudo Y., CYRIC annual report, 2012, 132, 135, 2013
Cyclotron and Radioisotope Center, Tohoku University, English

ヒトアストロサイトーマ由来細胞株1321N1におけるセロトニン取り込み機構について　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 飯田 智光, 谷内 一彦, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 22回・42回, 165, 165, Oct. 2012
日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese

HISTAMINE H-3 RECEPTOR REGULATES THE FUNCTIONS OF THE PANCREATIC beta-CELL
T. Nakamura, T. Yoshikawa, N. Noguchi, F. Naganuma, R. Harada, A. Mohsen, K. Yanai, INFLAMMATION RESEARCH, 61, S83, S83, Sep. 2012
English, Summary international conference

レチノイン酸／レチノイドの抗動脈硬化作用　　　　　　　　　　　　　　　
菅原明, 宇留野晃, 箱田明子, 清水恭子, 佐藤郁子, 松田謙, 壱岐裕子, 吉川雄朗, 工藤正孝, 伊藤貴子, 伊藤貞嘉, 東北大学医学部保健学科紀要, 21, 2, 61, 63, Jul. 2012
Japanese, Introduction research institution

脳 アルツハイマー病病理像を生体画像化するための光イメージングプローブの開発　　　　　　　　　　　　　　　
原田 龍一, 岡村 信行, 古本 祥三, 吉川 雄朗, 谷内 一彦, 工藤 幸司, JSMI Report, 5, 2, 35, 35, May 2012
日本分子イメージング学会, Japanese

波長依存性蛍光プローブによるアミロイド・タウの選択的検出　　　　　　　　　　　　　　　
原田 龍一, 岡村 信行, 古本 祥三, 吉川 雄朗, 谷内 一彦, 工藤 幸司, JSMI Report, 5, 2, 142, 142, May 2012
日本分子イメージング学会, Japanese

種々のレチノイドX受容体(RXR)アゴニストは、AtT20細胞の増殖・アポトーシス・POMC発現・ACTH分泌に異なる影響を及ぼす　　　　　　　　　　　　　　　
箱田明子, 宇留野晃, 清水恭子, 伊藤貴子, 吉川雄朗, 藤原幾磨, 松田謙, 工藤正孝, 影近弘之, 岩崎泰正, 伊藤貞嘉, 菅原明, ACTH RELATED PEPTIDES, 23, 15, 16, Mar. 2012, [Peer-reviewed]
Japanese

ヒトアストロサイトによるヒスタミン取り込み機構　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 中村 正帆, 井筒 敏恵, 谷内 一彦, 日本薬理学雑誌, 139, 1, 6P, 6P, Jan. 2012
(公社)日本薬理学会, Japanese

膵β細胞におけるヒスタミン3型受容体の発現とインスリン分泌での役割　　　　　　　　　　　　　　　
中村 正帆, 大杉 真也, 吉川 雄朗, 谷内 一彦, 日本薬理学雑誌, 139, 1, 10P, 10P, Jan. 2012
(公社)日本薬理学会, Japanese

PPARγと高血圧・動脈硬化
菅原明, 宇留野晃, 工藤正孝, 松田謙, 清水恭子, 吉川雄朗, 伊藤貴子, 箱田明子, 伊藤貞嘉, 東北大学医学部保健学科紀要, 21, 1, 1, 5, Jan. 2012
東北大学医学部保健学科, Japanese, Introduction research institution

臨床に役立つ神経薬理・化学 ヒスタミンと神経系 睡眠と覚醒　　　　　　　　　　　　　　　
吉川 雄朗, 谷内 一彦, Clinical Neuroscience, 30, 1, 8, 9, Jan. 2012
(株)中外医学社, Japanese

THE ROLE OF HISTAMINE RECEPTOR H3 IN PANCREATIC b-CELLS
T. Nakamura, T. Yoshikawa, N. Noguchi, M. Ohsugi, K. Yanai, Inflammation Research, 60, S2, S336, S336, Sep. 2011
Springer Science and Business Media LLC, English, Summary international conference

ヒトアストロサイトによるヒスタミン取り込み機構について(Important role of plasma membrane monoamine transporters in histamine uptake by human astrocytes)　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 中村 正帆, 井筒 敏恵, 谷内 一彦, 神経化学, 50, 2-3, 174, 174, Sep. 2011
日本神経化学会, English

膵β細胞に発現しているヒスタミン3型受容体はブドウ糖刺激インスリン分泌を抑制する　　　　　　　　　　　　　　　
中村 正帆, 吉川 雄朗, 大杉 真也, 長沼 史登, 野口 直哉, 谷内 一彦, 日本生化学会大会プログラム・講演要旨集, 84回, 4T15p, 15, Sep. 2011
(公社)日本生化学会, Japanese

Histamine Receptor H3 Regulates the Functions of Pancreatic [beta]-Cells
Tadaho Nakamura, Takeo Yoshikawa, Naoya Noguchi, Hiroshi Okamoto, Akira Sugawara, Kazuhiko Yanai, Diabetes, 60, Supplement_1, A539, A540, 01 Jul. 2011
American Diabetes Association, English, Summary international conference

Positron emission tomography evaluation of sedative properties of antihistamines
Kazuhiko Yanai, Dongying Zhang, Manabu Tashiro, Takeo Yoshikawa, Fumito Naganuma, Ryuichi Harada, Tadaho Nakamura, Katsuhiko Shibuya, Nobuyuki Okamura, EXPERT OPINION ON DRUG SAFETY, 10, 4, 613, 622, Jul. 2011
English, Book review

「ヒスタミン受容体」を理解する (Dermatology Today)　　　　　　　　　　　　　　　
谷内一彦, 長沼史登, 中村正帆, 吉川雄朗, Dermatology Today, 4, 4, 4, 12, 15 Apr. 2011
Japanese, Introduction scientific journal

薬物脳内移行性のPETによる測定 抗ヒスタミン薬を例に
谷内 一彦, 張 冬穎, 原田 龍一, 中村 正帆, 吉川 雄朗, 船木 善仁, 渋谷 勝彦, 古本 祥三, 田代 学, 岩田 錬, 岡村 信行, ナノ医工学年報, 4, 1, 119, 122, Mar. 2011
東北大学グローバルCOEプログラム「新世紀世界の成長焦点に築くナノ医工学拠点」, Japanese

ヒスタミンＨ１受容体占拠率による脳内移行性評価　　　　　　　　　　　　　　　
谷内一彦, 田代 学, 古本祥三, 吉川雄朗, 岡村信行, 創薬技術の革新 マイクロドーズからPET分子イメージングへの新展開, 147, 152, 2011
編集者 杉山雄一、山下伸二、栗原千絵子 メディカルドゥ社, Japanese, Introduction commerce magazine

【創薬研究への分子イメージング応用】 PET・PECT分子イメージングと医薬品開発 画像バイオマーカーとしての分子イメージングの利用 分子イメージングによる受容体占拠率の解析 (遺伝子医学MOOK)　　　　　　　　　　　　　　　
谷内一彦, 吉川雄朗, 古本祥三, 遺伝子医学MOOK, 18, 133, 139, Dec. 2010
Japanese, Introduction scientific journal

【創薬技術の革新 マイクロドーズからPET分子イメージングへの新展開】 PET分子イメージング マイクロドーズからバイオマーカー開発へ PETが着目する課題(個別課題) ヒスタミンH1受容体占拠率による脳内移行性評価 (遺伝子医学MOOK)　　　　　　　　　　　　　　　
谷内一彦, 田代学, 古本祥三, 吉川雄朗, 岡村信行, 遺伝子医学MOOK, 別冊, 創薬技術の革新 マイクロドーズからPET分子イメージングへの新展開, 147, 152, Oct. 2010
(株)メディカルドゥ, Japanese, Introduction scientific journal

【脳とアレルギー】 脳機能を標的とした新しい痒み治療戦略 痒みイメージング研究の視点から (アレルギー・免疫)　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 谷内一彦, アレルギー・免疫, 17, 11, 1868, 1873, Oct. 2010
Japanese, Introduction scientific journal

ヒスタミン受容体とストレス脆弱性(Histamine receptors and stress vulnerability)　　　　　　　　　　　　　　　
谷内 一彦, 吉川 雄朗, 櫻井 映子, 及川 綾子, 長沼 史登, 岡村 信行, 神経化学, 49, 2-3, 737, 737, Aug. 2010
日本神経化学会, English

内標準法によるヒスタミンと1-メチルヒスタミンの同時測定
長沼史登, 井筒敏恵, 張冬頴, 中村正帆, 原田龍一, 吉川雄朗, 岡村信行, 谷内一彦, 日本薬理学会北部会プログラム・抄録集, 61st, 2010

【花粉症の理想的治療法】 薬理学からみた理想的な抗ヒスタミン薬 (臨床免疫・アレルギー科)
吉川雄朗, 田代学, 岡村信行, 谷内一彦, 臨床免疫・アレルギー科, 52, 6, 623, 628, Dec. 2009
(有)科学評論社, Japanese, Introduction scientific journal

最近の話題 抗ヒスタミン薬と認知機能 dimebonはアルツハイマー病の認知機能を改善する (日本薬理学雑誌)　　　　　　　　　　　　　　　
谷内一彦, 吉川雄朗, 日本薬理学雑誌, 134, 4, 235, 235, Oct. 2009
Japanese, Introduction scientific journal

２型リアノジン受容体遺伝子にはGG-AG配列で切断されるイントロンが存在する　　　　　　　　　　　　　　　
池田崇之, 野口直哉, 吉川雄朗, 宇留野 晃, 那谷耕司, 高沢 伸, 岡本 宏, 米倉秀人, 菅原 明, 第82回日本生化学会大会プログラム・要旨集, 3T18a-6, 2009

FK506結合蛋白質ノックアウトマウスにおけるブドウ糖刺激インスリン分泌の低下　　　　　　　　　　　　　　　
吉川雄朗, 東北医学雑誌, 120, 1, 118, 121, Jun. 2008, [Invited]
Japanese

消化管がん細胞におけるチアゾリジン誘導体のREG遺伝子転写抑制および細胞増殖抑制効果　　　　　　　　　　　　　　　
山内晶世, 高橋巌, 桑名文二, 那谷耕司, 野口直哉, 池田崇之, 吉川雄朗, 小野川徹, 鈴木巌, 高沢伸, 岡本宏, 日本薬学会126年会講演要旨集, 2, 99, 99, 2006

消化管がん細胞におけるREG (Regenerating gene)遺伝子の発現　　　　　　　　　　　　　　　
高沢 伸, 山内晶世, 高橋 巌, 小野川 徹, 池田崇之, 秋山貴子, 野口直哉, 那谷耕司, 吉川雄朗, 岡本 宏, Cancer Science, 95, 429-429, 429, 2004
(一社)日本癌学会, Japanese

創薬技術の革新 マイクロドーズからPET分子イメージングへの新展開　　　　　　　　　　　　　　　
杉山雄一, 山下伸二, 栗原千絵子, d, 谷内一彦, 田代学, 古本祥三, 吉川雄朗, 岡村信行, ヒスタミンＨ１受容体占拠率による脳内移行性評価, 147-152
メディカルドゥ, 20 Oct. 2010, Japanese, Scholarly book, [Joint work]

ヒスタミン神経系を標的とした創薬研究について　　　　　　　　　　　　　　　
吉川雄朗
2024年度脳科学研究教育センター合宿研修, 10 Nov. 2024

視床下部外側ニューロテンシン神経の覚醒調節における重要性の検討　　　　　　　　　　　　　　　
長沼史登, 平野匡佑, 中村正帆, Ramalingam Vetrivelan, 吉川雄朗
第75回日本薬理学会北部会, 21 Sep. 2024

過眠症治療におけるヒスタミン代謝酵素阻害薬の有効性評価　　　　　　　　　　　　　　　
吉川雄朗, Girgin Birkan、Agu Anne, 平野匡佑, 長澤翔太, 岩渕好治, 中村正帆, 谷内一彦, 望月貴年, 柳沢正史, 長沼史登
第75回日本薬理学会北部会, 21 Sep. 2024, Oral presentation

Evaluation of histamine N-methyltransferase inhibition on sleep- wake behavior in wild-type and narcolepsy model mice　　　　　　　　　　　　　　　
Anne Bernadette Agu, Fumito Naganuma, Birkan Girgin, Kyosuke Hirano, Takatoshi Mochizuki, Masashi Yanagisawa, Takeo Yoshikawa
第37回北海道薬物作用談話会, 18 Aug. 2024, Oral presentation

Evaluation of Therapeutic Potential for Histamine N-methyltransferase Inhibitior in Narcolepsy　　　　　　　　　　　　　　　
Birkan Girgin, Fumito Naganuma, Anne Bernadette Agu, Tadaho Nakamura, Takatoshi Mochizuki, Takeo Yoshikawa
Neuro2024, 26 Jul. 2024, Poster presentation

Inhibition of histamine metabolizing enzyme in the brain reduces cataplexy in narcolepsy model mice　　　　　　　　　　　　　　　
Takeo Yoshikawa, Birkan Girgin, Anne Bernadette Agu, Tadaho Nakamura, Kazuhiko Yanai, Takatoshi Mochizuki, Shota Nagasawa, Yoshiharu Iwabuchi, Fumito Naganuma
35th World Congress Collegium Internationale Neuro-Psychopharmacologicum, 25 May 2024, Poster presentation

ヒスタミン代謝酵素阻害薬の薬理作用について　　　　　　　　　　　　　　　
吉川雄朗, Birkan Girgin, Anne Bernadette Agu, 谷内一彦, 中村正帆, 長沼史登
第24回日本ヒスタミン学会, 17 Feb. 2024, Oral presentation

ナルコレプシーに対する創薬を目指して　　　　　　　　　　　　　　　
吉川雄朗
蔵王カンファレンス, 26 Jan. 2024, Keynote oral presentation
[Invited]

ヒスタミン代謝酵素阻害薬のナルコレプシー治療に対する有用性の検討　　　　　　　　　　　　　　　
長沼史登, Birkan Girgin, Anne Bernadette S. Agu, 中村正帆, 谷内一彦, 吉川雄朗
第30回日本時間生物学会学術大会, 16 Sep. 2023, Poster presentation

ナルコレプシー治療におけるヒスタミン 代謝酵素阻害薬の重要性について　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, Girgin Birkan, 谷内一彦, 中村正帆
第7回黒潮カンファレンス, 12 Jul. 2023, Oral presentation

炎症シグナルによるグルコース応答性転写因子ChREBPの機能制御メカニズムの解明　　　　　　　　　　　　　　　
横山 敦, 野呂 英理香, 岡本 好司, 吉川 雄朗, 島 弘季, 五十嵐 和彦, 菅原 明
内分泌代謝学サマーセミナー, 06 Jul. 2023

薬理学ロールプレイの学習目標到達度：ルーブリック自己評価を用いた検討　　　　　　　　　　　　　　　
中村正帆, 木村武司, 長沼史登, 吉川雄朗, 岡村信行, 柳田俊彦
第96回日本薬理学会年会, 03 Dec. 2022

視床下部外側ニューロテンシン神経は睡眠覚醒サイクルに重要である　　　　　　　　　　　　　　　
長沼史登, 中村正帆, ベトリベラン・ラマリンガム, 吉川雄朗, 岡村信行
第96回日本薬理学会年会, 02 Dec. 2022

ヒスタミン代謝酵素阻害剤メトプリンの行動薬理学的検討　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 長谷茜音, 谷内一彦, 中村正帆
第73回日本薬理学会北部会, 18 Sep. 2022, Oral presentation

脳内ヒスタミン濃度と脳機能との関連について　　　　　　　　　　　　　　　
吉川雄朗
第23回応用薬理シンポジウム, 10 Sep. 2022, Nominated symposium

扁桃体中心核ニューロテンシン神経細胞の睡眠覚醒サイクルにおける役割の検討
中村 正帆, 長沼 史登, 田中 聖人, 井上 まり絵, 直野 留美, 吉川 雄朗, 岡村 信行
応用薬理, Aug. 2022, 応用薬理研究会, Japanese
Aug. 2022 - Aug. 2022

ブドウ糖代謝におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
吉川 雄朗, 松澤 拓郎, 谷内 一彦, 山口 祐
糖尿病, Apr. 2022, (一社)日本糖尿病学会, Japanese
Apr. 2022 - Apr. 2022

神経細胞に発現するヒスタミン代謝酵素の重要性について　　　　　　　　　　　　　　　
吉川雄朗, 小松由梨香, 松澤健介, 大塚里奈, 長沼史登, 中村正帆, 谷内一彦
第95回日本薬理学会年会, 07 Mar. 2022
07 Mar. 2022

ヒスタミン3型受容体は膵β細胞機能を抑制している　　　　　　　　　　　　　　　
久冨宇太, 松澤拓郎, 中村正帆, 谷内一彦, 吉川雄朗
第95回日本薬理学会年会, 07 Mar. 2022

肝細胞特異的ヘパラン硫酸欠損マウスはインスリン感受性が亢進する　　　　　　　　　　　　　　　
松澤拓郎, 小玉菜穂, 久冨宇太, 谷内一彦, 吉川雄朗
第95回日本薬理学会年会, 07 Mar. 2022

経口ヒスチジン摂取は脳内ヒスタミン神経系を活性化させることで記憶能を向上させる　　　　　　　　　　　　　　　
盧優慈, 中村正帆, 長沼史登, 谷内一彦, 吉川雄朗
第95回日本薬理学会年会, 07 Mar. 2022

脳内ヒスタミン代謝酵素の機能解析　　　　　　　　　　　　　　　
吉川雄朗, 小松由梨香, 松澤健介, 大塚里奈, 長沼史登, 中村正帆, 谷内一彦
第23回日本ヒスタミン学会, 08 Jan. 2022

膵臓β細胞特異的ヒスタミン3型受容体欠損マウスの解析　　　　　　　　　　　　　　　
久冨宇太, 松澤拓郎, 中村正帆, 谷内一彦, 吉川雄朗
第23回日本ヒスタミン学会, 07 Jan. 2022

ヒスタミン神経細胞特異的な活性変化が攻撃行動と睡眠覚醒サイクルに及ぼす影響　　　　　　　　　　　　　　　
中村正帆, 長沼史登, 黒柳浩志, 田中聖人, 吉川雄朗, 谷内一彦, 岡村信行
日本ヒスタミン学会プログラム・講演要旨集, 2022
2022 - 2022

中脳水道周辺灰白質へ投射するヒスタミン神経は神経因性疼痛を緩和する　　　　　　　　　　　　　　　
長沼史登, 長沼史登, 梅ゆう, 松澤拓郎, 中村正帆, 中村正帆, 岡村信行, 岡村信行, 谷内一彦, 吉川雄朗
日本ヒスタミン学会プログラム・講演要旨集, 2022
2022 - 2022

白色脂肪細胞機能におけるヘパラン硫酸の重要性について　　　　　　　　　　　　　　　
松澤 拓郎, 守田 匡伸, 谷内 一彦, 吉川 雄朗
日本生化学会大会プログラム・講演要旨集, Nov. 2021, (公社)日本生化学会, Japanese
Nov. 2021 - Nov. 2021

ブドウ糖代謝組織におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
松澤拓郎, 横山眞理子, 谷内一彦, 吉川雄朗
第40回日本糖質学会年会, 27 Oct. 2021

ヘパラン硫酸は白色脂肪細胞の分化を促進し、インスリン感受性を高める　　　　　　　　　　　　　　　
松澤拓郎, 守田匡伸, 入江史敏, 山口祐, 谷内一彦, 吉川雄朗
第15回東北糖鎖研究会, 25 Sep. 2021

白色脂肪細胞におけるヘパラン硫酸はインスリン感受性を亢進することで糖恒常性維持に寄与している　　　　　　　　　　　　　　　
松澤拓郎, 守田匡伸, 谷内一彦, 吉川雄郎
第87回日本生化学会 東北支部会, May 2021

膵β細胞におけるグルコース応答性転写因子ChREBPの機能制御因子の探索　　　　　　　　　　　　　　　
横山 敦, 野呂 英理香, 岡本 好司, 松澤 拓郎, 吉川 雄朗, 島 弘季, 五十嵐 和彦, 菅原 明
日本内分泌学会雑誌, Apr. 2021, (一社)日本内分泌学会, Japanese
Apr. 2021 - Apr. 2021

四塩化炭素誘発性肝細胞障害に対するヘパラン硫酸の保護的効果について　　　　　　　　　　　　　　　
松澤 拓郎, 島根 彩衣, 谷内 一彦, 吉川 雄朗
第94回日本薬理学会年会, 10 Mar. 2021

ワイヤレス給電を用いた集団飼育マウスの長期自発行動および体温測定機器開発　　　　　　　　　　　　　　　
谷内 一彦, 吉川 雄朗, 相良 健一, 佐々木 秀
第94回日本薬理学会年会, 10 Mar. 2021

ヒスタミン代謝酵素阻害剤の探索研究　　　　　　　　　　　　　　　
吉川 雄朗, 大塚 里奈, 佐藤 夕季, 谷内 一彦
第94回日本薬理学会年会, 10 Mar. 2021

アストロサイトに発現するヒスタミン代謝酵素は自発行動量と覚醒状態を制御する　　　　　　　　　　　　　　　
大塚 里奈, 長沼 史登, 佐藤 夕季, 高橋 佑奈, 谷内 一彦, 吉川 雄朗
第94回日本薬理学会年会, 08 Mar. 2021

Histamine activation of periaqueductal grey matter and somatosensory cortex exerts an antinociceptive effect in mechanical allodynia　　　　　　　　　　　　　　　
梅 煜, 吉川 雄朗, 長沼 史登, 谷内 一彦
第94回日本薬理学会年会, 08 Mar. 2021

薬理学的知識に基づいた抗ヒスタミン薬の選び方〜効き目を科学し、理解し、伝えましょう〜　　　　　　　　　　　　　　　
吉川雄朗
看護薬理学カンファレンス, 07 Mar. 2021, Invited oral presentation
[Invited]

ブドウ糖代謝におけるヘパラン硫酸の重要性について　　　　　　　　　　　　　　　
吉川雄朗
第67回日本臨床検査医学会学術集会, Nominated symposium
19 Nov. 2020 - 22 Nov. 2020, [Invited]

アストロサイトによる脳内ヒスタミン系制御の重要性について　　　　　　　　　　　　　　　
大塚里奈, 吉川雄朗, 長沼史登, 佐藤夕季, 高橋佑奈, 谷内一彦
第71回日本薬理学会北部会, 04 Sep. 2020, Oral presentation

Histaminergic activation of periaqueductal grey matter and somatosensory cortex relieves mechanical allodynia in nerve-injury model mice.　　　　　　　　　　　　　　　
Mei Yu, Takeo Yoshikawa, Fumito Naganuma, Kazuhiko Yanai
第71回日本薬理学会北部会, 04 Sep. 2020, Oral presentation

成体マウス脳内のヒスタミン減少により、うつ様行動の増加、記憶能の低下、自発行 動量の減少が惹起される　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 山田瑶, 吉川貴子, 大隅典子, 谷内一彦
NPBPPP2020合同年会, Oral presentation
21 Aug. 2020 - 23 Aug. 2020

成体マウス脳内のヒスタミン減少により、うつ様行動の増加、記憶能の低下、自発行動量の減少が惹起される　　　　　　　　　　　　　　　
吉川 雄朗, 長沼 史登, 山田 瑶, 吉川 貴子, 大隅 典子, 谷内 一彦
日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集, Aug. 2020, 日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会, Japanese
Aug. 2020 - Aug. 2020

医学部学生に対してイオントラップの概念を理解するためのアスピリンを用いた薬物動態学実習　　　　　　　　　　　　　　　
佐藤岳哉、斎藤将樹、吉川雄朗、長沼史登、中村正帆、岡村信行、柳澤輝行、谷内一彦
第93回日本薬理学会年会, 16 Mar. 2020, Nominated symposium
16 Mar. 2020 - 18 Mar. 2020

高血糖状態におけるミクログリア機能異常　　　　　　　　　　　　　　　
大塚 里奈、飯田 智光、吉川 雄朗、谷内 一彦
第93回日本薬理学会年会, 18 Mar. 2020, Poster presentation

へパラン硫酸による筋分化促進作用は、骨格筋機能維持に必須である。　　　　　　　　　　　　　　　
横山 眞理子、吉川 雄朗、松澤 拓郎、山口 祐、谷内 一彦
第93回日本薬理学会年会, 17 Mar. 2020, Oral presentation

ヒスタミンH3受容体逆作動薬は中脳水道周辺灰白質のヒスタミンH1受容体とH2受容体を活性化して、神経因性疼痛の症状を緩和する　　　　　　　　　　　　　　　
梅 煜、吉川 雄朗、松澤 拓郎、齊藤 秀俊、谷内 一彦
第93回日本薬理学会年会, 17 Mar. 2020, Poster presentation

神経細胞およびアストロサイト特異的ヒスタミンH1受容体欠損マウスの解析　　　　　　　　　　　　　　　
吉川 雄朗、Karpati Aniko、長沼 史登、松澤 拓郎、谷内 一彦
第93回日本薬理学会年会, 17 Mar. 2020, Oral presentation

成熟マウスにおける慢性ヒスタミン減少はうつ様行動と睡眠障害を惹起する　　　　　　　　　　　　　　　
山田 瑶、吉川 雄朗、長沼 史登、谷内 一彦
第93回日本薬理学会年会, 16 Mar. 2020, Oral presentation

ワイヤレス給電と体内埋め込み型センサーを用いた新しい動物行動薬理学　　　　　　　　　　　　　　　
谷内 一彦、吉川 雄朗、相良 健一、佐々木 秀
第93回日本薬理学会年会, 16 Mar. 2020, Poster presentation

アストロサイトに発現するヒスタミン代謝酵素の役割について　　　　　　　　　　　　　　　
高橋 佑奈、吉川 雄朗、大塚 里奈、谷内 一彦
第93回日本薬理学会年会, 16 Mar. 2020, Poster presentation

ヒスタミン神経細胞の薬理遺伝学的活性化が睡眠覚醒に及ぼす影響　　　　　　　　　　　　　　　
中村正帆、長沼史登、黒柳浩志、田中聖人、吉川雄朗、谷内一彦、 岡村信行
第22回日本ヒスタミン学会, 02 Feb. 2020, Oral presentation

成体マウス脳内の慢性的ヒスタミン減少は、うつ様行動の増加及び 自発行動量の減少を惹起する　　　　　　　　　　　　　　　
山田瑶、吉川雄朗、長沼史登、谷内一彦
第22回日本ヒスタミン学会, 01 Feb. 2020, Oral presentation

アストロサイト特異的ヒスタミン代謝酵素欠損マウスの表現型解析　　　　　　　　　　　　　　　
高橋佑奈、吉川雄朗、谷内一彦
第22回日本ヒスタミン学会, 01 Feb. 2020, Oral presentation

経口デスロラタジンの脳内ヒスタミンH1受容体結合 陽電子放出断層撮影を用いたin vivoランダム割付二重盲検クロスオーバー臨床試験　　　　　　　　　　　　　　　
中村 正帆, 平岡 宏太良, 原田 龍一, 松澤 拓郎, 吉川 雄朗, 長沼 史登, 田代 学, 谷内 一彦, 岡村 信行
臨床薬理, Nov. 2019, (一社)日本臨床薬理学会, Japanese
Nov. 2019 - Nov. 2019

Histamine H3 Receptor Antagonist Enhances Histamine Levels in Periaqueductal Grey Matter and Ameliorates Mechanical Allodynia via Histamine H1 and H2 Receptors　　　　　　　　　　　　　　　
Takeo Yoshikawa, Yu Mei, Takuro Matsuzawa, Hidetoshi Tozaki-Saitoh, Kazuhiko Yanai
6th Congress of Asian College of Neuropyschopharmacology, 11 Oct. 2019, English, Poster presentation
[International presentation]

ヘパラン硫酸による糖代謝制御機構の解明　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 谷内一彦
第70回日本薬理学会北部会, 20 Sep. 2019, Japanese, Invited oral presentation
[Domestic Conference]

脳内ヒスタミン減少による成熟マウスでの行動変化について　　　　　　　　　　　　　　　
山田瑶, 吉川雄朗, 長沼史登, 谷内一彦
第70回日本薬理学会北部会, 20 Sep. 2019, Japanese, Oral presentation
[Domestic Conference]

骨格筋におけるヘパラン硫酸の機能解明　　　　　　　　　　　　　　　
横山眞理子, 吉川雄朗, 松澤拓郎, 山口祐, 谷内一彦
第13回東北糖鎖研究会, 06 Sep. 2019, Japanese, Poster presentation
[Domestic Conference]

糖代謝関連臓器におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
吉川雄朗, 松澤拓郎, 横山眞理子, 菅原明, 山口祐, 谷内一彦
第13回東北糖鎖研究会, 06 Sep. 2019, Japanese, Oral presentation
[Domestic Conference]

膵β細胞におけるグルコース応答性転写因子ChREBPの機能制御因子の探索　　　　　　　　　　　　　　　
横山 敦, 野呂 英理香, 松澤 拓郎, 吉川 雄朗, 島 弘季, 五十嵐 和彦, 菅原 明
日本生化学会大会プログラム・講演要旨集, Sep. 2019, (公社)日本生化学会, Japanese
Sep. 2019 - Sep. 2019

Histamine H1 receptors on astrocytes regulate aggressive behaviour, circadian rhythm, and wakefulness in mice　　　　　　　　　　　　　　　
Aniko Karpati, Takeo Yoshikawa, Fumito Naganuma, Kazuhiko Yanai
Neuro2019, 25 Jul. 2019, English, Poster presentation
[Domestic Conference]

Involvement of Astrocyte Histamine H1 Receptors in the Regulation of Behavior　　　　　　　　　　　　　　　
Karpati A, Yoshikawa T, Yanai K
XIV European Meeting on Glial Cells in Health and Disease, GLIA 2019, 11 Jul. 2019, English, Poster presentation
[International presentation]

肥満細胞は脳内ヒスタミン量を調節して覚醒を引き起こす　　　　　　　　　　　　　　　
酒井 紀彰, 八木 櫻子, 吉川 雄朗, 小野 太輔, 西紋 昌平, 久保 允人, 谷内 一彦, 西野 精治
日本睡眠学会定期学術集会プログラム・抄録集, Jun. 2019, (一社)日本睡眠学会, Japanese
Jun. 2019 - Jun. 2019

Histamine H1 receptor occupancy measured by PET in the human brain after oral administration of desloratadine　　　　　　　　　　　　　　　
Nakamura T, Yoshikawa T, Tashiro M, Okamura N, Yanai K
48th meeding of the European Histamine Research Society, 16 May 2019, English, Poster presentation
[International presentation]

Histamine N-Methyltransferase in the Brain　　　　　　　　　　　　　　　
Yoshikawa T, Nakamura T, Yanai K
48th Meeting of the European Histamine Research Society, 16 May 2019, English, Invited oral presentation
[Invited], [International presentation]

無細胞蛋白合成系を用いたタンパク質の部位特異的フッ素18標識法　　　　　　　　　　　　　　　
谷内 一彦, 原田 龍一, 谷内 亜衣, 吉川 雄朗, 古本 祥三, 岩田 錬
JSMI Report, May 2019, 日本分子イメージング学会, Japanese
May 2019 - May 2019

無細胞蛋白合成系を用いたタンパク質の部位特異的フッ素18標識法　　　　　　　　　　　　　　　
谷内 一彦, 原田 龍一, 谷内 亜衣, 吉川 雄朗, 古本 祥三, 岩田 錬
JSMI Report, May 2019, 日本分子イメージング学会, Japanese
May 2019 - May 2019

白色脂肪細胞におけるヘパラン硫酸は糖の恒常性の維持に重要である　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 谷内 一彦
糖尿病, Apr. 2019, (一社)日本糖尿病学会, Japanese
Apr. 2019 - Apr. 2019

Affibodyの新規18F標識法によるHER2、PD-L1発現腫瘍の分子イメージング　　　　　　　　　　　　　　　
谷内 亜衣, 原田 龍一, 岩田 錬, 吉川 雄朗, 古本 祥三, 谷内 一彦, 内藤 剛, 海野 倫明, 亀井 尚, 石田 孝宜
日本外科学会定期学術集会抄録集, Apr. 2019, (一社)日本外科学会, Japanese
Apr. 2019 - Apr. 2019

白色脂肪細胞におけるヘパラン硫酸は糖の恒常性の維持に重要である　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 谷内 一彦
糖尿病, Apr. 2019, (一社)日本糖尿病学会, Japanese
Apr. 2019 - Apr. 2019

Affibodyの新規18F標識法によるHER2、PD-L1発現腫瘍の分子イメージング　　　　　　　　　　　　　　　
谷内 亜衣, 原田 龍一, 岩田 錬, 吉川 雄朗, 古本 祥三, 谷内 一彦, 内藤 剛, 海野 倫明, 亀井 尚, 石田 孝宜
日本外科学会定期学術集会抄録集, Apr. 2019, (一社)日本外科学会, Japanese
Apr. 2019 - Apr. 2019

骨格筋分化におけるヘパラン硫酸の機能解明　　　　　　　　　　　　　　　
吉川雄朗, 横山眞理子, 松澤拓郎, 谷内一彦
第９２回日本薬理学会年会, 15 Mar. 2019, Japanese, Oral presentation
[Domestic Conference]

マウス線維芽細胞3T3-L1および白色脂肪細胞におけるヘパラン硫酸の重要性について　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 谷内一彦
第９２回日本薬理学会年会, 14 Mar. 2019, Japanese, Poster presentation
[Domestic Conference]

アデノ随伴ウイルスを用いた脳内ヒスタミン合成酵素の機能解析　　　　　　　　　　　　　　　
山田瑶, 吉川雄朗, 長沼史登, 谷内一彦
第９２回日本薬理学会年会, 14 Mar. 2019, Japanese, Poster presentation
[Domestic Conference]

ハイスループットスクリーニング系を用いたHNMT特異的阻害剤の探索　　　　　　　　　　　　　　　
北野陽菜, 吉川雄朗, 谷内一彦
第９２回日本薬理学会年会, 14 Mar. 2019, Japanese, Poster presentation
[Domestic Conference]

ヒスチジンの疲労感低減機能に関する研究　　　　　　　　　　　　　　　
笹原 育子, 安居 昌子, 杉田 麻友, 柴草 哲郎, 藤村 尚子, 野沢 与志津, 吉川 雄朗, 谷内 一彦
アミノ酸研究, Feb. 2019, 日本アミノ酸学会, Japanese
Feb. 2019 - Feb. 2019

Brain histamine H₁ receptor occupancy measured by PET after oral administration of desloratadine and loratadine
Nakamura Tadaho, Hiraoka Kotaro, Harada Ryuchi, Matsuzawa Takuro, Yoshikawa Takeo, Tashiro Manabu, Yanai Kazuhiko, Okamura Nobuyuki
Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2019, Japanese Pharmacological Society, Japanese
2019 - 2019,

Objective: Some histamine H₁ receptor (H₁R) antagonists have sedative effects, caused by the blockade of histamine neural transmission. Desloratadine is a newly-marked antihistamine, but its sedative properties have not been examined by positron emission tomography (PET). We examined the brain H₁R binding potential ratio (BPR), H₁R occupancy (H₁RO) and the subjective sleepiness after oral administration of desloratadine and loratadine, the prodrug of desloratadine.

Methods: Eight healthy male volunteers underwent PET imaging with [¹¹C]doxepin after single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPRs and H₁ROs in the cerebral cortices were calculated. Subjective sleepiness was quantified by the LARS and the SSS.

Results: BPR after loratadine administration was significantly lower than placebo (p<0.05), but BPR after desloratadine was not significant. There was no significant difference, however, between H₁RO after desloratadine and loratadine administration. The subjective sleepiness was not significantly different among the two antihistamines and placebo.

Conclusion: At therapeutic dose, desloratadine did not bind significantly to brain H₁Rs and did not cause significant sedation.

Important role fo heparan sulfate in skeletal muscles　　　　　　　　　　　　　　　
Takeo Yoshikawa, Mariko Yokoyama, Takuro Matsuzawa, Kazuhiko Yanai
American society of cell biology 2018 meeting, 10 Dec. 2018, English, Poster presentation
[International presentation]

脳内ヒスタミン除去機構を標的とした創薬研究：ヒスタミン代謝酵素HNMTの機能解明と阻害剤探索　　　　　　　　　　　　　　　
吉川雄朗, 北野陽菜, 谷内一彦
第48回日本神経精神薬理学会, 14 Nov. 2018, Japanese, Poster presentation
[Domestic Conference]

アンバーコドンを用いた無細胞蛋白質合成法による新規18F標識法タンパク質合成法の開発　　　　　　　　　　　　　　　
原田 龍一, 谷内 亜衣, 岩田 錬, 吉川 雄朗, 石川 洋一, 古本 祥三, 谷内 一彦
核医学, Nov. 2018, (一社)日本核医学会, Japanese
Nov. 2018 - Nov. 2018

脳内ヒスタミン除去機構を標的とした創薬研究 ヒスタミン代謝酵素HNMTの機能解明と阻害剤探索　　　　　　　　　　　　　　　
吉川 雄朗, 北野 陽菜, 谷内 一彦
日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, Nov. 2018, 日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese
Nov. 2018 - Nov. 2018

脳内ヒスタミン系を標的とした創薬研究について　　　　　　　　　　　　　　　
吉川 雄朗, 谷内 一彦
第3回黒潮カンファレンス, 14 Oct. 2018, Japanese, Nominated symposium
[Invited], [Domestic Conference]

Cardio-facio-cutaneous症候群における成長障害の研究 -疾患モデルマウスによる胃・食道病変の解析-　　　　　　　　　　　　　　　
井上晋一, 高原真吾, 吉川雄朗, 新堀哲也, 谷内一彦, 松原洋一, 青木洋子
日本人類遺伝学会 第63回大会, 10 Oct. 2018, Japanese, Oral presentation
[Domestic Conference]

糖尿病モデルマウスにおけるミクログリア機能解析　　　　　　　　　　　　　　　
大塚里奈, 飯田智光, 吉川雄朗, 谷内一彦
第69回日本薬理学会北部会, 21 Sep. 2018, Japanese, Oral presentation
[Domestic Conference]

糖代謝におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
吉川 雄朗, 松澤 拓郎, 谷内 一彦
第69回日本薬理学会北部会, 21 Sep. 2018, Japanese, Public symposium
[Domestic Conference]

骨格筋組織におけるヘパラン硫酸の機能解析　　　　　　　　　　　　　　　
吉川雄朗, 横山眞理子, 松澤拓郎, 谷内一彦
第37回日本糖質学会, 28 Aug. 2018, Japanese, Poster presentation
[Domestic Conference]

Histamine clearance through polyspecific transporters and histamine N-methyltransferase in the brain　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Kazuhiko Yanai
World Histamine Symposium (WHS2018), 07 Jul. 2018, English, Nominated symposium
[Invited], [International presentation]

IMPORTANCE OF H1 AND H2 RECEPTORS IN PERIAQUEDUCTAL GRAY FOR JNJ10181457-INDUCED PAIN RELIEF　　　　　　　　　　　　　　　
Takuro Matsuzawa, Takeo Yoshikawa, Maria Mogilevskaya, Kazuhiko Yanai
World Histamine Symposium (WHS2018), 07 Jul. 2018, English, Poster presentation
[International presentation]

【遺伝子改変マウスを用いた新しい創薬・薬理学研究の展開】新規遺伝子ノックアウトマウスを用いた脳内ヒスタミンクリアランス系の解明　　　　　　　　　　　　　　　
吉川 雄朗, 中村 正帆, 谷内 一彦
日本薬理学雑誌, Jul. 2018, (公社)日本薬理学会, Japanese
Jul. 2018 - Jul. 2018, ヒスタミンは脳内では神経伝達物質として機能している。ヒスタミン神経は視床下部後部に位置する結節乳頭核に細胞体を有し、その神経線維を脳全体に投射する。これまでの研究により、ヒスタミン神経系の機能低下が様々な神経疾患と関連している可能性が示された。我々はシナプス間隙に放出されたヒスタミンの除去機構を抑制することで、ヒスタミン神経系を活性化し神経疾患の治療へと結びつけたいと考え、未解明の課題であったヒスタミンのクリアランス機構の解明に着手した。まず初代培養ヒトアストロサイトを用いた研究を行い、細胞外のヒスタミンがorganic cation transporter(OCT)3およびplasma membrane monoamine transporter(PMAT)によって細胞内へと輸送され、その後histamine N-methyltransferase(HNMT)によって不活化される、という分子機構を明らかにした。次にHNMTの生体における役割を明らかにするため、HNMT欠損マウスを新規に作製し、表現型を解析した。その結果、HNMTが脳内ヒスタミン濃度制御において中心的な役割を担っていることが示された。またHNMT欠損によりヒスタミンが異常高値となると、ヒスタミンH2受容体を介して高い攻撃性が惹起されること、H1受容体を介して睡眠覚醒サイクルに異常を来すことも明らかとなった。OCT3とPMATの脳内における役割については、セロトニン神経系やドパミン神経系との関連は報告されているものの、ヒスタミン神経系におけるこれらのトランスポーターの役割については不明な点が多い。現在我々はPMAT欠損マウスの表現型解析、およびHNMT阻害薬探索研究を行っている。今後トランスポーターとヒスタミン神経系との関連を解明することや中枢ヒスタミン系を標的とした創薬に尽力していきたいと考えている。(著者抄録)

Importance of heparan sulfate in adipose tissue　　　　　　　　　　　　　　　
Matsuzawa T, Yoshikawa T, Yanai K
18th world congress of basic and clinical pharmacology, 01 Jul. 2018, English, Poster presentation
[International presentation]

Important Role of Heparan Sulfate in Skeletal Mscules　　　　　　　　　　　　　　　
Yoshikawa T, Mogi A, Miura Y, Matsuzawa T, Yanai K
18th world congress of basic and clinical pharmacology, 01 Jul. 2018, English, Poster presentation
[International presentation]

Heparan sulfate in beta-cells regulates insulin secretion and contributes to normal glucose homeostasis　　　　　　　　　　　　　　　
Matsuzawa T, Yoshikawa T, Sugawara A, Yanai K
American Diabetes Association, 78th scientific sessions, 22 Jun. 2018, English, Poster presentation
[International presentation]

【神経系のトランスポーター-Up to date】トランスポーターの基礎 モノアミントランスポーター　　　　　　　　　　　　　　　
吉川 雄朗, 北野 陽菜, 谷内 一彦
Clinical Neuroscience, Jun. 2018, (株)中外医学社, Japanese
Jun. 2018 - Jun. 2018

Inhibitory effects of H3R inverse agonist/antagonist on microglial functions　　　　　　　　　　　　　　　
Iida T, Yoshikawa T, Yanai K
European Histamine Research Society 47the Annual Meeting, 30 May 2018, English, Oral presentation
[International presentation]

脂肪組織におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 谷内一彦
第61回日本糖尿病学会年次学術集会, 24 May 2018, Japanese, Poster presentation
[Domestic Conference]

筋芽細胞株C2C12および筋組織におけるヘパラン硫酸の役割　　　　　　　　　　　　　　　
横山眞理子, 吉川雄朗, 松澤拓郎, 谷内一彦
日本生化学会東北支部第84回例会, 19 May 2018, Japanese, Poster presentation
[Domestic Conference]

白色脂肪細胞におけるヘパラン硫酸は糖の恒常性維持に重要である　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 谷内一彦
日本生化学会東北支部第84会例会, 19 May 2018, Japanese, Poster presentation
[Domestic Conference]

Affibodyの新規18F標識法によるHER2発現乳癌の分子イメージング　　　　　　　　　　　　　　　
谷内 亜衣, 原田 龍一, 岩田 錬, 吉川 雄朗, 古本 祥三, 谷内 一彦, 石田 孝宣
日本乳癌学会総会プログラム抄録集, May 2018, (一社)日本乳癌学会, Japanese
May 2018 - May 2018

脂肪組織におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 谷内 一彦
糖尿病, Apr. 2018, (一社)日本糖尿病学会, Japanese
Apr. 2018 - Apr. 2018

低出力パルス波超音波の全脳照射はマウスの認知症モデルにおいて認知機能障害を改善する-内皮型NO合成酵素の重要性-　　　　　　　　　　　　　　　
江口久美子, 伊藤健太, 進藤智彦, 尾形剛, 加賀谷裕太, 黒澤亮, 門間雄斗, 一條貞満, 吉川雄朗, 谷内一彦, 瀧宏文, 金井浩, 大隅典子, 下川宏明
日本酸化ストレス学会学術集会プログラム・抄録集, 2018
2018 - 2018

ヒスタミン3型受容体インバースアゴニストはミクログリア機能を抑制しうつ様行動を改善する　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 谷内一彦
21 Dec. 2017, Oral presentation
[Domestic Conference]

がん原遺伝子Brafの活性化はマウス食道の拡張と前胃上皮の過増殖をもたらす　　　　　　　　　　　　　　　
井上 晋一, 高原 真吾, 吉川 雄朗, 新堀 哲也, 谷内 一彦, 松原 洋一, 青木 洋子
生命科学系学会合同年次大会, Dec. 2017, 生命科学系学会合同年次大会運営事務局, Japanese
Dec. 2017 - Dec. 2017

膵β細胞におけるヘパラン硫酸はインスリン分泌及び糖の恒常性維持に重要である　　　　　　　　　　　　　　　
松澤 拓郎, 吉川 雄朗, 中村 正帆, 谷内 一彦
生命科学系学会合同年次大会, Dec. 2017, 生命科学系学会合同年次大会運営事務局, Japanese
Dec. 2017 - Dec. 2017

ヒスタミン3型受容体インバースアゴニストによるミクログリア機能抑制について　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 谷内一彦
28 Sep. 2017, Poster presentation
[Domestic Conference]

脳内ヒスタミン神経系の過剰な興奮はH2受容体を介してマウスの攻撃性を増加させる　　　　　　　　　　　　　　　
吉川雄朗, 飯田智光, 長沼史登, 中村正帆, 岡村信行, 谷内一彦
第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会, 28 Sep. 2017, Oral presentation
札幌, [Domestic Conference]

フェルラ酸のαシヌクレインの凝集・線維化に対する阻害効果の検討　　　　　　　　　　　　　　　
陳梦格, 原田龍一, 吉川雄朗, 工藤幸司, 岡村信行, 谷内一彦
第68回日本薬理学会北部会, 15 Sep. 2017, Oral presentation
[Domestic Conference]

吸入麻酔薬の意識消失作用におけるヒスタミン受容体の役割　　　　　　　　　　　　　　　
民井亨, 中村正帆, 吉川雄朗, 長沼史登, 飯田智光, Karpati Aniko, 松澤拓郎, 北野陽菜, 山内正憲, 岡村信行, 谷内一彦
第68回日本薬理学会北部会, 15 Sep. 2017, Oral presentation
[Domestic Conference]

ヒスタミン-N-メチルトランスフェラーゼのin vivo機能解析　　　　　　　　　　　　　　　
中村 正帆, 吉川 雄朗, 岡村 信行
第68回日本薬理学会北部会, 15 Sep. 2017, Oral presentation
[Domestic Conference]

Neurotransmitter histamine positively affects astrocyte signaling and gliotransmitter release　　　　　　　　　　　　　　　
Karpati Aniko, 飯田 智光, 吉川 雄朗
第68回日本薬理学会北部会, 15 Sep. 2017, Oral presentation
[Domestic Conference]

骨格筋におけるヘパラン硫酸の役割について　　　　　　　　　　　　　　　
吉川雄朗, 茂木明日香, 松澤拓郎, 三浦大和, 中村正帆, 谷内一彦
第68回日本薬理学会北部会, 15 Sep. 2017, Oral presentation
山形, [Domestic Conference]

脳に効くヒスチジン摂取　　　　　　　　　　　　　　　
吉川雄朗
第60回日本神経化学学会, 07 Sep. 2017, Invited oral presentation
仙台, [Domestic Conference]

ヒスタミン3型受容体インバースアゴニストによるミクログリア機能抑制について(Suppression of microglial functions by an H3R inverse agonist)　　　　　　　　　　　　　　　
飯田 智光, 吉川 雄朗, 谷内 一彦
日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, Sep. 2017, 日本生物学的精神医学会・日本神経精神薬理学会, English
Sep. 2017 - Sep. 2017

ミクログリア機能におけるヒスタミンの重要性　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 中村正帆, 谷内一彦
第40回日本神経科学大会, 20 Jul. 2017, Oral presentation
千葉, [Domestic Conference]

マウスOCT2、OCT3、PMATの機能解析　　　　　　　　　　　　　　　
吉川雄朗, 三浦大和, 茂木明日香, 谷内一彦
第12回トランスポーター研究年会, 08 Jul. 2017, Poster presentation
仙台, [Domestic Conference]

THE EFFECT OF H3 RECEPTOR ANTAGONIST ON NEUROPATHIC PAIN　　　　　　　　　　　　　　　
T Nakamura, T Matsuzawa, M Mogilevskaya, A Mogi, T Yoshikawa, F Naganuma, N Okamura, K Yanai
Histamine 2017, 11 May 2017, Poster presentation
Netherlands アムステルダム, [International presentation]

糸球体足細胞特異的Extl3欠損マウスを用いた糸球体チャージバリアの検討
青木聡, 箱田明子, 吉川雄朗, 松阪泰二, 佐藤博, 伊藤貞嘉, 菅原明
日本腎臓学会誌, 25 Apr. 2017, Japanese
25 Apr. 2017 - 25 Apr. 2017

新規遺伝子ノックアウトマウスを用いた脳内ヒスタミンクリアランス系の解明　　　　　　　　　　　　　　　
吉川雄朗, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Public symposium
JAPAN 長崎, [Domestic Conference]

Histamine induced gliotransmitter release from cortical rat astrocytes　　　　　　　　　　　　　　　
Aniko Karpati, 吉川雄朗, 中村正帆, 長沼史登, 飯田智光, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Oral presentation
JAPAN 長崎, [Domestic Conference]

膵β細胞におけるヘパラン硫酸はインスリン分泌や籐の恒常性維持に重要である　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 中村正帆, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Oral presentation
JAPAN 長崎, [Domestic Conference]

時間分解蛍光法ランタニド錯体標識βシートリガンドの開発　　　　　　　　　　　　　　　
原田龍一, 岡村信行, 古本祥三, 吉川雄朗, 工藤幸司, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Oral presentation
JAPAN 長崎, [Domestic Conference]

ヒスタミンH3受容体によるミクログリア機能の重要性　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Oral presentation
JAPAN 長崎, [Domestic Conference]

デスフルラン麻酔におけるヒスタミン受容体の役割　　　　　　　　　　　　　　　
民井亨, 中村正帆, 吉川雄朗, 長沼史登, 飯田智光, Karpati Aniko, 松澤拓郎, 北野陽奈, 岡村信行, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Poster presentation
JAPAN 長崎, [Domestic Conference]

神経障害性疼痛に対するヒスタミンH3受容体拮抗薬の効果　　　　　　　　　　　　　　　
吉川雄朗, 松澤拓郎, 茂木明日香, Maria Mogilevskaya, 中村正帆, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Poster presentation
JAPAN 長崎, [Domestic Conference]

骨格筋におけるヘパラン硫酸欠損による筋力や運動能の低下　　　　　　　　　　　　　　　
茂木明日香, 吉川雄朗, 三浦大和, 松澤拓郎, 谷内一彦
第90回日本薬理学会年会, 15 Mar. 2017, Poster presentation
JAPAN 長崎, [Domestic Conference]

神経障害性疼痛におけるヒスタミンH3受容体（H3R）拮抗薬の作用について　　　　　　　　　　　　　　　
松澤拓郎, Mogilevskaya Maria, 吉川雄朗, 中村正帆, 谷内一彦
第20回日本ヒスタミン学会, 24 Nov. 2016, Oral presentation
JAPAN 倉敷, [Domestic Conference]

Histamine promotes gliotransmitter release from astrocytes　　　　　　　　　　　　　　　
Karpati A, Yoshikawa T, Nakamura T, Naganuma F, Iida T, Yanai K
Society for Neuroscience, 14 Nov. 2016, English, Poster presentation
[International presentation]

Importance of Histamine Clearance for Brain Functions　　　　　　　　　　　　　　　
Yoshikawa T, Naganuma F, Nakamura T, Iida T, Karpati A, Mochizuki T, Yanai K
Society for Neuroscience, 14 Nov. 2016, English, Poster presentation
[International presentation]

神経障害性疼痛におけるヒスタミン3型受容体の役割について　　　　　　　　　　　　　　　
松澤拓郎, Mogilevskaya Maria, 吉川雄朗, 中村正帆, 谷内一彦
第67回日本薬理学会北部会, 30 Sep. 2016, Oral presentation
札幌, [Domestic Conference]

膵β細胞特異的Ｅｘｔ１ノックアウトマウスの解析　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 中村正帆, 谷内一彦
第67回日本薬理学会北部会, 30 Sep. 2016, Oral presentation
札幌, [Domestic Conference]

ニューロン新生マーカー・BrdUの脳内分布における拡散型ヌクレオシドトランスポーター1の役割の解明　　　　　　　　　　　　　　　
木村隼也, 吉田寛伸, 竹生田淳, Bastos Gilmara, 鈴木登紀子, 吉川雄朗, 根元瓦, 中川西修, 丹野孝一, 谷内一彦, 平澤典保健, 守屋孝洋
第67回日本薬理学会北部会, 30 Sep. 2016, Oral presentation
札幌, [Domestic Conference]

Role of histamine neurons in isoflurane anesthesia.　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Aniko Karpati, Toru Tamii, Nobuyuki Okamura, Kazuiko Yanai
第39回日本神経科学大会, 20 Jul. 2016, Poster presentation
横浜, [Domestic Conference]

Importance of histamine N-methyltransferase in brain functions　　　　　　　　　　　　　　　
Takeo Yoshikawa, Fumito Naganuma, Tadaho Nakamura, Takatoshi Mochizuki, Tomomitsu Iida, Aniko Karpati, Takuro Matsuzawa, Kazuhiko Yanai
第39回日本神経科学大会, 20 Jul. 2016, Poster presentation
横浜, [Domestic Conference]

Astrocytes elevate glutamate release in response to histamine　　　　　　　　　　　　　　　
Anikó Kárpáti, Takeo Yoshikawa, Tadaho Nakamura, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Kazuhiko Yanai
第39回日本神経科学大会, 20 Jul. 2016, Poster presentation
横浜, [Domestic Conference]

Histamine N-methyltransferase is important for the normal sleep-wake cycles and aggression through the regulation of brain histamine concentration.　　　　　　　　　　　　　　　
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Kazuhiko Yanai
30th CINP world congress of neuropsychopharmacology, 03 Jul. 2016, Poster presentation
Republic of Korea ソウル, [International presentation]

Interactions between histaminergic neuronal system and isoflurane anesthesia in mice　　　　　　　　　　　　　　　
Toru Tamii, Tadaho Nakamura, Takeo Yoshikawa, Osamu Kobayashi, Masanori Yamauchi, Kazuiko Yanai
日本麻酔科学会第63回学術集会, 26 May 2016, Poster presentation
福岡, [Domestic Conference]

Electroencephalogram of H1KO mice under isoflurane anesthesia.　　　　　　　　　　　　　　　
Tadaho, Nakamura, Takeo Yoshikawa, Fumito Naganuma, Tomomitsu Iida, Aniko Karpati, Toru Tamii, Nobuyuki Okamura, Kazuiko Yanai
European Histamine Research Society 45th annual meeting, 11 May 2016, Poster presentation
Italy Florence, [International presentation]

Role of brain histamine in glutamate release from cultured astrocytes　　　　　　　　　　　　　　　
Aniko Karpati, 吉川雄朗, 中村正帆, 長沼史登, 飯田智光, 三浦大和, 谷内一彦
第89回日本薬理学会年会, 09 Mar. 2016, Oral presentation
横浜, [Domestic Conference]

マウスにおけるヒスタミン神経系とイソフルラン麻酔の相互作用について　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 長沼史登, 飯田智光, 三浦大和, Aniko Karpati, 望月貴年, 谷内一彦
第89回日本薬理学会年会, 09 Mar. 2016, Oral presentation
横浜, [Domestic Conference]

Histamine N-methyltransferaseの欠損はマウスにおいて睡眠覚醒サイクル異常と高い攻撃性を引き起こす　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 堀米愛, 三浦大和, 矢内敦, 望月貴年, 谷内一彦
第89回日本薬理学会年会, 09 Mar. 2016, Oral presentation
横浜, [Domestic Conference]

膵β細胞におけるヘパラン硫酸の重要性　　　　　　　　　　　　　　　
松澤拓郎, 吉川雄朗, 中村正帆, 谷内一彦
第89回日本薬理学会年会, 09 Mar. 2016, Poster presentation
横浜, [Domestic Conference]

ヒスタミンによるミクログリア機能制御について　　　　　　　　　　　　　　　
吉川雄朗, 飯田智光, 松澤拓郎, 中村正帆, 谷内一彦
第38回日本分子生物学会年会第88回日本生化学会合同大会, 01 Dec. 2015, Poster presentation
神戸, [Domestic Conference]

Role of histaminergic neuronal system in isoflurane anesthesia　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Osamu Kobayashi, Miho Kaneko, Masanori Yamauchi, Kazuhiko Yanai
Anesthesiology 2015, 24 Oct. 2015, Poster presentation
United States San Diego, [International presentation]

Histamine N-methyltransferseノ欠損はマウスにおいて攻撃性を高め、睡眠サイクル異常を引き起こす　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 堀米愛, 三浦大和, 中村正帆, 矢内敦, 望月貴年, 谷内一彦
第37回日本生物学的精神医学会第45回日本精神神経薬理学会, 24 Sep. 2015, Oral presentation
東京, [Domestic Conference]

生体内ミクログリアにおける中枢ヒスタミン系の役割　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 松澤拓郎, 長沼史登, 中村正帆, 三浦大和, 谷内一彦
第66回日本薬理学会北部会, 18 Sep. 2015, Oral presentation
富山, [Domestic Conference]

イソフルランの麻酔作用におけるヒスタミン神経系の役割　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 長沼史登, 三浦大和, 飯田智光, 松澤拓郎, 堀米愛, Karpati Aniko, 谷内一彦
第66回日本薬理学会北部会, 18 Sep. 2015, Oral presentation
富山, [Domestic Conference]

Histamine N-methyltransferase deficiency induced the abnormal sleep-awake cycles and aggressive behavior in mice　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 矢内敦, 堀米愛, 三浦大和, 中村正帆, 望月貴年, 谷内一彦
第58回日本神経化学大会, 11 Sep. 2015, Oral presentation
大宮, [Domestic Conference]

ヒスタミン研究に残された解決されるべき課題：脳内ヒスタミンの分解系を中心に　　　　　　　　　　　　　　　
谷内一彦, 長沼史登, 中村正帆, 岡村信行, 吉川雄朗
第19回活性アミンに関するワークショップ, 20 Aug. 2015, Invited oral presentation
いわき, [Domestic Conference]

マウス多基質性トランスポーターによるモノアミン輸送能の検討　　　　　　　　　　　　　　　
三浦大和, 吉川雄朗, 長沼史登, 中村正帆, 飯田智光, 谷内一彦
第19回活性アミンに関するワークショップ, 20 Aug. 2015, Oral presentation
いわき, [Domestic Conference]

Mechanism of brain histamine clearance　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 三浦大和, 矢内敦, 堀米愛, 中村正帆, 望月貴年, 谷内一彦
第38回日本神経科学大会, 28 Jul. 2015, Poster presentation
神戸, [Domestic Conference]

Role of histamine in gliotransmitter release from astrocytes　　　　　　　　　　　　　　　
Aniko Karpati, Takeo Yoshikawa, Tadaho Nakamura, Fumito Naganuma, Tomomitsu Iida, Yamato Miura, Kazuhiko Yanai
第38回日本神経科学大会, 28 Jul. 2015, Poster presentation
神戸, [Domestic Conference]

無細胞蛋白質合成法を用いたIL8受容体のPETイメージング　　　　　　　　　　　　　　　
吉川雄朗, 原田龍一, 古本祥三, 渋谷勝彦, 岩田錬, 谷内一彦
日本生化学会東北支部第81回例会, 09 May 2015, Poster presentation
仙台, [Domestic Conference]

脳内ヒスタミンのクリアランス機構について　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 三浦大和, 矢内敦, 堀米愛, 中村正帆, 望月貴年, 谷内一彦
日本生化学会東北支部第81回例会, 09 May 2015, Oral presentation
仙台, [Domestic Conference]

Analysis of histamine N-methyltransferase deficient mice　　　　　　　　　　　　　　　
Naganuma F, Yoshikawa T, Nakamura T, Miura Y, Matsuzawa T, Yanai K
European Histamine Research Society 44th annual meeting, 06 May 2015, Oral presentation
Spain Malaga, [Domestic Conference]

H1-knocked out mouse had high sensitivity to isoflurane anesthesia　　　　　　　　　　　　　　　
Nakamura T, Yoshikawa T, Naganuma F, iida T, Miura Y, Yanai K
European Histamine Research Society 44th annual meeting, 06 May 2015, Poster presentation
Spain Malaga, [Domestic Conference]

種々のレチノイドX受容体アゴニストは、AtT20細胞の増殖・アポトーシス・Pomc発現・ACTH分泌に異なる影響を及ぼす　　　　　　　　　　　　　　　
箱田明子, 宇留野晃, 清水恭子, レハナ・パービン, 横山敦, 吉川雄朗, 工藤正孝, 影近弘之, 岩崎泰正, 伊藤貞嘉, 菅原 明
第88回日本内分泌学会学術総会, 23 Apr. 2015, Poster presentation
東京, [Domestic Conference]

Histamine N-methyltransferase ノックアウトマウスの解析　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 三浦大和, 柳生彩乃, 中村正帆, 谷内一彦
第88回日本薬理学年会, 18 Mar. 2015, Oral presentation
名古屋, [Domestic Conference]

イソフルラン麻酔における神経ヒスタミンとヒスタミンH1受容体の役割　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 長沼史登, 飯田智光, 三浦大和, 谷内一彦
第88回日本薬理学年会, 18 Mar. 2015, Poster presentation
名古屋, [Domestic Conference]

骨格筋特異的Ext1欠損マウスの解析　　　　　　　　　　　　　　　
三浦大和, 吉川雄朗, 中村正帆, 長沼史登, 飯田智光, 谷内一彦
第88回日本薬理学年会, 18 Mar. 2015, Oral presentation
名古屋, [Domestic Conference]

Histamine N-methyltransferaseノックアウトマウスの行動解析　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 三浦大和, 堀米愛, 谷内一彦
第24回神経行動薬理若手研究者の集い, 17 Mar. 2015, Oral presentation
名古屋, [Domestic Conference]

脳内ヒスタミン研究におけるマイクロダイアリシスの使用について　　　　　　　　　　　　　　　
吉川雄朗, 中村正帆, 長沼史登, 三浦大和, 谷内一彦
第２５回マイクロダイアリシス研究会, 20 Dec. 2014, Invited oral presentation
東京, [Domestic Conference]

グリア細胞とヒスタミンとの関連について　　　　　　　　　　　　　　　
吉川雄朗
2014年度包括脳ネットワーク冬のシンポジウム, 11 Dec. 2014, Poster presentation
東京, [Domestic Conference]

高血糖刺激は副腎11β-水酸化酵素遺伝子（CYP11B1）の発現を誘導する　　　　　　　　　　　　　　　
菅原香織, 小暮直敬, 松田 謙, 宇留野晃, 佐藤郁子, 清水恭子, レハナ・パービン, 島田洋樹, 吉川雄朗, 工藤正孝, 箱田明子, 伊藤 亮, 横山 敦, 伊藤貞嘉, 菅原 明
第37回日本高血圧学会総会, 17 Oct. 2014, Poster presentation
横浜, [Domestic Conference]

高血糖刺激による副腎アルドステロン合成酵素遺伝子（CYP11B2）発現亢進の分子機構　　　　　　　　　　　　　　　
小暮直敬, 菅原香織, 松田 謙, 宇留野晃, 佐藤郁子, 清水恭子, レハナ・パービン, 島田洋樹, 吉川雄朗, 工藤正孝, 箱田明子, 伊藤 亮, 横山 敦, 伊藤貞嘉, 菅原 明
第37回日本高血圧学会総会, 17 Oct. 2014, Poster presentation
横浜, [Domestic Conference]

マウスにおける低親和性トランスポーターの輸送能解析　　　　　　　　　　　　　　　
三浦大和, 吉川雄朗, 長沼史登, 中村正帆, 谷内一彦
第18回日本ヒスタミン学会, 10 Oct. 2014, Oral presentation
尼崎, [Domestic Conference]

Histamine N-methyl transferaseノックアウトマウスの解析　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 三浦大和, 中村正帆, 谷内一彦
第18回日本ヒスタミン学会, 10 Oct. 2014, Oral presentation
尼崎, [Domestic Conference]

低ヒスチジン食によりマウス脳内ヒスタミン含量が減少し、不安様行動が惹起される　　　　　　　　　　　　　　　
吉川雄朗, 中村正帆, 柴草哲朗, 杉田麻友, 長沼史登, 飯田智光, 三浦大和, モフセンアタイエブ, 原田龍一, 谷内一彦
第18回日本ヒスタミン学会, 10 Oct. 2014, Oral presentation
尼崎, [Domestic Conference]

無細胞蛋白質合成法を用いたPETイメージングプローブ作製　　　　　　　　　　　　　　　
吉川雄朗, 原田龍一, 古本祥三, 渋谷勝彦, 岩田錬, 谷内一彦
第65回日本薬理学会北部会, 26 Sep. 2014, Oral presentation
福島, [Domestic Conference]

ヒスタミン代謝酵素欠損マウスの解析　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 三浦大和, 柳生彩乃, 谷内一彦
第65回日本薬理学会北部会, 26 Sep. 2014, Oral presentation
福島, [Domestic Conference]

Expression and Function of Histamine H3 receptor in Pancreatic Islets　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Kazuhiko Yanai
17th world congress of basic & clinical pharmacology, 13 Jul. 2014, Poster presentation
South Africa Cape Town, [International presentation]

The mechanism of monoamine transport by human astrocytes　　　　　　　　　　　　　　　
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Yamato Miura, Kazuhiko Yanai
17th world congress of basic & clinical pharmacology, 13 Jul. 2014, Poster presentation
South Africa Cape Town, [International presentation]

Generation of a stable H295R cell line expressing 11β-hydroxylase gene promoter and the effect of high-glucose on its expression　　　　　　　　　　　　　　　
Kaori Sugawara, Ken Matsuda, Naotaka Kogure, Akira Uruno, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa, Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
16th international congress of endocrinology, 21 Jun. 2014, Oral presentation
United States Chicago, [International presentation]

High-glucose stimulates aldosterone synthase gene (CYP11B2) expression via the induction of T-type calcium channels in H295R cells　　　　　　　　　　　　　　　
Naotaka Kogure, Ken Matsuda, Akira Uruno, Kaori Sugawara, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa, Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
16th international congress of endocrinology, 21 Jun. 2014, Oral presentation
United States Chicago, [International presentation]

Generation of a Stable H295R Cell Line Expressing 11beta-Hydroxylase Gene Promoter and the Effect of High-Glucose on Its Expression　　　　　　　　　　　　　　　
Sugawara Kaori, Matsuda Ken, Kogure Naotaka, Uruno Akira, Sato Ikuko, Shimizu Kyoko, Parvin Rehana, Yoshikawa Takeo, Kudo Masataka, Saito-Hakoda Akiko, Ito Ryo, Yokoyama Atsushi, Ito Sadayoshi, Sugawara Akira
ENDOCRINE REVIEWS, Jun. 2014
Jun. 2014 - Jun. 2014

High-Glucose Stimulates Aldosterone Synthase Gene (CYP11B2) Expression Via the Induction of T-Type Calcium Channels in H295R Cells　　　　　　　　　　　　　　　
Naotaka Kogure, Ken Matsuda, Akira Uruno, Kaori Sugawara, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa, Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
ENDOCRINE REVIEWS, Jun. 2014, ENDOCRINE SOC, English
Jun. 2014 - Jun. 2014

The inhibitory effect of histamine in mouse primary microglia　　　　　　　　　　　　　　　
Iida T, Yoshikawa T, Asami Y, Naganuma F, Miura Y, Nakamura T, Mohsen A, Iwata R, Yanai K
European histamine research society 43rd annual meeting, 07 May 2014, Oral presentation
France Lyon, [International presentation]

Analysis of mouse polyspecific transporters　　　　　　　　　　　　　　　
Miura Y, Yoshikawa T, Naganuma F, Nakamura T, Iida T, Harada R, Mohsen A, Yanai K
European histamine research society 43rd annual meeting, 07 May 2014, Poster presentation
France Lyon, [International presentation]

Importance of histidine intake for histaminergic nervous system　　　　　　　　　　　　　　　
Miura Y, Yoshikawa T, Shibakusa T, Sugita M, Yanai K
European histamine research society 43rd annual meeting, 07 May 2014, Oral presentation
France Lyon, [International presentation]

マウス初代培養ミクログリアにおけるヒスタミンの役割　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 浅見雄太, 中村正帆, 長沼史登, 原田龍一, 岩田錬, 谷内一彦
第87回日本薬理学会年会, 19 Mar. 2014, Oral presentation
仙台, [Domestic Conference]

膵ランゲルハンス島アルファ細胞におけるヒスタミンH3受容体の役割　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 長沼史登, 飯田智光, 三浦大和, 谷内一彦
第87回日本薬理学会年会, 19 Mar. 2014, Oral presentation
仙台, [Domestic Conference]

ヒトアストロサイトにおけるモノアミン取り込み機構の解明　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 飯田智光, 三浦大和, 谷内一彦
第87回日本薬理学会年会, 19 Mar. 2014, Oral presentation
仙台, [Domestic Conference]

食餌中に含まれるヒスチジンはヒスタミン神経系に必須である　　　　　　　　　　　　　　　
吉川雄朗, 柴草哲朗, 杉田麻友, モフセン・アタイエブ, 長沼史登, 谷内一彦
第87回日本薬理学会年会, 19 Mar. 2014, Poster presentation
仙台, [Domestic Conference]

マウス多特異性トランスポーターの機能解析　　　　　　　　　　　　　　　
三浦大和, 吉川雄朗, 長沼史登, 中村正帆, モフセン・アタイエブ, 飯田智光, 谷内一彦
第87回日本薬理学会年会, 19 Mar. 2014, Poster presentation
仙台, [Domestic Conference]

低親和性モノアミントランスポーターの機能解析　　　　　　　　　　　　　　　
三浦大和, 吉川雄朗, 谷内一彦
第7回リトリート大学院生研究発表会, 18 Jan. 2014, Poster presentation
仙台, [Domestic Conference]

ヒトアストロサイトによるモノアミン取り込み機構　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 飯田智光, 三浦大和, 谷内一彦
第7回リトリート大学院生研究発表会, 18 Jan. 2014, Poster presentation
仙台, [Domestic Conference]

マウス初代培養ミクログリアにおけるヒスタミンの役割　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 谷内一彦
第7回リトリート大学院生研究発表会, 18 Jan. 2014, Poster presentation
仙台, [Domestic Conference]

マウス初代培養ミクログリアにおけるヒスタミンの役割について　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 長沼史登, 中村正帆, 三浦大和, 岩田錬, 谷内一彦
第17回日本ヒスタミン学会, 21 Nov. 2013, Oral presentation
松江, [Domestic Conference]

Plasma membrane monoamine transporter is important for monoamine uptake in a human astrocytoma-derived cell line, 1321N1 cells　　　　　　　　　　　　　　　
Naganuma F, Yoshikawa T, Nakamura T, Yanai K
7th east asian consortium on biomedical engineering, 18 Nov. 2013, Oral presentation
Taiwan 台北, [International presentation]

The role of histamine receptors in pancreatic alpha-cells　　　　　　　　　　　　　　　
Nakamura T, Yoshikawa T, Naganuma F, Harada R, Yanai K
7th east asian consortium on biomedical engineering, 18 Nov. 2013, Oral presentation
Taiwan 台北, [International presentation]

ヒトアストロサイトーマ由来細胞株1321N1はPMATを介してモノアミンを取り込む　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 谷内一彦
第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会 合同大会, 24 Oct. 2013, Oral presentation
沖縄, [Domestic Conference]

睡眠剥奪ストレスに惹起される不安様行動は、ヒスタミン摂取により低減される　　　　　　　　　　　　　　　
長沼史登, Attayeb Mohsen, 吉川雄朗, 谷内一彦
第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会 合同大会, 24 Oct. 2013, Oral presentation
沖縄, [Domestic Conference]

ヒスタミンはヒスタミンH3受容体を介してミクログリアの機能を抑制する　　　　　　　　　　　　　　　
飯田智光, 吉川雄朗, 根東明広, 長沼史登, 中村正帆, 三浦大和, 岩田錬, 谷内一彦
第64回日本薬理学会北部会, 13 Sep. 2013, Oral presentation
旭川, [Domestic Conference]

低親和性モノアミントランスポーターの機能解析　　　　　　　　　　　　　　　
三浦大和, 吉川雄朗, 長沼史登, 中村正帆, 飯田智光, 谷内一彦
第64回日本薬理学会北部会, 13 Sep. 2013, Oral presentation
旭川, [Domestic Conference]

RXRアゴニストHX630のCushing病新規治療薬としての可能性　　　　　　　　　　　　　　　
小暮直敬, 箱田明子, 宇留野晃, 清水恭子, 菅原香織, 壹岐裕子, 吉川雄朗, 松田謙, 工藤正孝, 影近弘之, 岩崎泰正, 伊藤貞嘉, 菅原明
第49回高血圧関連疾患モデル学会学術総会, 06 Sep. 2013, Oral presentation
東京, [Domestic Conference]

グリア細胞とヒスタミン　　　　　　　　　　　　　　　
吉川雄朗
2013年度 包括脳ネットワーク夏のワークショップ, 29 Aug. 2013, Nominated symposium
名古屋, [Domestic Conference]

Low histamine diet increases anxiogenic like behavior in chronic sleep deprived mice　　　　　　　　　　　　　　　
Attayeb Mohsen, Takeo Yoshikawa, Kazuhiko Yanai
Neuro2013, 20 Jun. 2013, Oral presentation
京都, [Domestic Conference]

Development of PET imaging tracer for in vivo detection of Tau pathology in Alzheimer's disease　　　　　　　　　　　　　　　
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Teturo Tago, Takeo Yoshikawa, Hiroyuki Arai, Ren Iwata, Yukitsuk kudo, Kazuhiko Yanai
NIH Tohoku University JSPS symposium, 09 May 2013, Poster presentation
JAPAN 仙台, [International presentation]

Dietary histamine is functioning against stress vulnerability induced by chronic sleep deprivation　　　　　　　　　　　　　　　
Attayeb Mohsen, Takeo Yoshikawa, Kazuhiko Yanai
NIH Tohoku University JSPS symposium, 09 May 2013, Poster presentation
JAPAN 仙台, [International presentation]

Histamine inhibits phagocytosis and morphological change in mouse primary microglia　　　　　　　　　　　　　　　
Tomomitsu Iida, Takeo Yoshikawa, Akihiro Kondo, Fumito Naganuma, Tadaho Nakamura, Ren Iwata, Kazuhiko Yanai
NIH Tohoku University JSPS symposium, 09 May 2013, Poster presentation
JAPAN 仙台, [International presentation]

The role of histamine receptors on glucagon secretion in αTC1.6 cell　　　　　　　　　　　　　　　
T Nakamura, T, Yoshikawa, F Naganuma, R Harada, A Mohsen,K Yanai
42nd European Histamine Research Society Annual Meeting, 08 May 2013, Oral presentation
Poland Lodz, [International presentation]

Histamine transport by mouse plasma membrane monoamine transporter and mouse organic cation transporter 3　　　　　　　　　　　　　　　
F Naganuma,T, Yoshikawa, T, Nakamura, T Iida, R Harada,A Mohsen, K Yanai
42nd European Histamine Research Society Annual Meeting, 08 May 2013, Oral presentation
Poland Lodz, [International presentation]

High-glucose stimulates aldosterone synthase gene (CYP11B2) expression via T-type calcium channel in human adrenal H295R cells　　　　　　　　　　　　　　　
Akira Sugawara, Takako Saito-Ito, Naotaka Kogure, Kaori Sugawara, Ken Matsuda, Akira Uruno, Ikuko Sato, Kyoko Shimizu, Yuko Iki, Takeo Yoshikawa, Masataka Kudo, Akiko Saito-Hakoda, Sadayoshi Ito
The 6th international aldosterone forum in Japan, 21 Apr. 2013, Poster presentation
JAPAN, [International presentation]

Histamine Inhibited Phagocytosis of the Primary Mouse Microglia　　　　　　　　　　　　　　　
Tomomitsu Iida, Takeo Yoshikawa, Akihiro Kondo, FUmito Naganuma, Tadaho Nakamura, Attayeb Mohsen, Ren Iwata, Kazuhiko Yanai
6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering, 23 Mar. 2013, Oral presentation
Singapore, [International presentation]

CHronic Sleep Deprivation Impacts on Behaviors in Mice　　　　　　　　　　　　　　　
Attayeb Mohsen, Takeo Yoshikawa, Tadaho Nakamura, Fumito Naganuma, Tomomitsu Iida, Kazuhiko Yanai
6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering, 23 Mar. 2013, Oral presentation
Singapore, [International presentation]

アストロサイトにおけるモノアミン取り込みにはPMATが重要な役割を果たしている　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 飯田智光, 谷内一彦
第86回日本薬理学会年会, 21 Mar. 2013, Oral presentation
福岡, [Domestic Conference]

マウス自発行動及び不安様行動における睡眠剥奪ストレスとヒスタミンの効果について　　　　　　　　　　　　　　　
Mohsen Attayeb, 吉川雄朗, 谷内一彦
第86回日本薬理学会年会, 21 Mar. 2013, Oral presentation
福岡, [Domestic Conference]

タウイメージングプローブ候補化合物18F標識アリールキノリン誘導体の前臨床評価　　　　　　　　　　　　　　　
原田龍一, 岡村信行, 古本祥三, 多胡哲郎, 吉川雄朗, 荒井啓行, 岩田錬, 谷内一彦, 工藤幸司
第86回日本薬理学会年会, 21 Mar. 2013, Oral presentation
福岡, [Domestic Conference]

ヒトアストロサイトによるヒスタミン除去メカニズムの解明　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 飯田智光, 中村正帆, 笠島敦子, 笹野公伸, 谷内一彦
第86回日本薬理学会年会, 21 Mar. 2013, Poster presentation
福岡, [Domestic Conference]

グルカゴン産生α細胞株TC1.6におけるヒスタミンの役割　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 谷内一彦
第86回日本薬理学会年会, 21 Mar. 2013, Poster presentation
福岡, [Domestic Conference]

Plasma membrane monoamine transporter (PMAT) is important for monoamine clearance by human astrocytoma-derived cell line.,1321N1 cells　　　　　　　　　　　　　　　
Fumito Naganuma, Takeo Yoshikawa, Tomomitsu Iida, kazuhiko Yanai
The 21st Korea-Japan joint seminar on pharmacology, 31 Oct. 2012, Poster presentation
Republic of Korea Jeju, [International presentation]

ヒトアストロサイトによるヒスタミン除去機構について　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 飯田智光, 中村正帆, 笠島敦子, 笹野公伸, 谷内一彦
第16回日本ヒスタミン学会, 19 Oct. 2012, Oral presentation
JAPAN 岡山, [Domestic Conference]

ヒトアストロサイトーマ由来細胞株1321N1におけるセロトニン取り込み機構について　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 飯田智光, 谷内一彦
第22回日本臨床精神神経薬理学会第42回日本神経精神薬理学会合同大会, 18 Oct. 2012, Oral presentation
JAPAN 宇都宮, [Domestic Conference]

高血糖刺激はアルドステロン合成酵素遺伝子（CYP11B2）の発現を増強する　　　　　　　　　　　　　　　
伊藤貴子, 松田謙, 宇留野晃, 佐藤郁子, 清水恭子, 壱岐裕子, 吉川雄朗, 工藤正孝, 箱田明子, 伊藤貞嘉, 菅原晃
第16回日本内分泌病理学会, 11 Oct. 2012, Oral presentation
JAPAN, [Domestic Conference]

種々のRXRアゴニストがAtT20細胞増殖・アポトーシス・POMC発現・ACTH分泌に及ぼす影響　　　　　　　　　　　　　　　
箱田明子, 宇留野晃, 清水恭子, 伊藤貴子, 吉川雄朗, 藤原幾磨, 松田謙, 佐藤郁子, 壱岐裕子, 工藤正孝, 影近弘之, 岩崎泰正, 伊藤貞嘉, 菅原明
第16回日本内分泌病理学会, 11 Oct. 2012, Oral presentation
JAPAN 仙台, [Domestic Conference]

ニコチンがヒト冠動脈血管内皮細胞の遺伝子発現に及ぼす影響ならびにそれに対するACE阻害薬・ＡＲＢの効果　　　　　　　　　　　　　　　
工藤正孝, 松田謙, 伊藤貴子, 宇留野晃, 清水恭子, 吉川雄朗, 箱田明子, 伊藤貞嘉, 菅原明
第35回日本高血圧学会総会, 20 Sep. 2012, Poster presentation
JAPAN 名古屋, [Domestic Conference]

高血糖刺激はヒト副腎H295R細胞におけるアルドステロン合成酵素遺伝子の発現を増強する　　　　　　　　　　　　　　　
伊藤貴子, 松田謙, 宇留野晃, 清水恭子, 吉川雄朗, 工藤正孝, 箱田明子, 伊藤貞嘉, 菅原明
第35回日本高血圧学会総会, 20 Sep. 2012, Poster presentation
JAPAN 名古屋, [Domestic Conference]

Plasma membrane monoamine transporterはヒトアストロサイトにおけるドパミン不活化に重要である　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 飯田智光, 中村正帆, 谷内一彦
第35回日本神経科学大会, 18 Sep. 2012, Oral presentation
JAPAN 名古屋, [Domestic Conference]

小動物PET/CTを用いた抗ヒスタミン薬レボセチリジンの鎮静性評価　　　　　　　　　　　　　　　
飯田智光, 船木善仁, 石渡喜一, 長沼史登, 原田龍一, 吉川雄朗, 古本祥三, 岩田錬, 谷内一彦
第63回日本薬理学会北部会, 14 Sep. 2012, Oral presentation
JAPAN 新潟, [Domestic Conference]

ヒトアストロサイトーマ由来細胞株1321N1細胞におけるセロトニン取り込み機構の解明　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 飯田智光, 谷内一彦
第63回日本薬理学会北部会, 14 Sep. 2012, Oral presentation
JAPAN 新潟, [Domestic Conference]

Mechanism of histamine clearance by primary human astrocytes　　　　　　　　　　　　　　　
T Yoshikawa, F Naganuma, T Iida, T Nakamura, K Yanai
包括型脳科学研究推進支援ネットワーク 夏のワークショップ, 24 Jul. 2012, Poster presentation
JAPAN 仙台, [Domestic Conference]

ヒトアストロサイトによるヒスタミン不活化機構の解明　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 飯田智光, 谷内一彦
第7回トランスポーター研究会年会, 09 Jun. 2012, Poster presentation
JAPAN 京都, [Domestic Conference]

Human Astrocytes transport histamine through plasma membrane monoamine transporter　　　　　　　　　　　　　　　
T Yoshikawa, F Naganuma, T Nakamura, T Iida, R harada, A Mohsen, K Yanai
41st Annual Meeting of the European Histamine Research Society, 02 May 2012, Oral presentation
Belfast, [International presentation]

Histamine H3 receptor regulates the functions of pancreatic ß-cells　　　　　　　　　　　　　　　
T Nakamura, T Yoshikawa, N Noguchi, F Naganuma, R Harada, A Mohsen, K Yanai
41st Annual Meeting of the European Histamine Research Society., 02 May 2012, Oral presentation
Belfast, [International presentation]

高血糖刺激によるアルドステロン合成酵素（CYP11B2）の発現増強効果　　　　　　　　　　　　　　　
松田 謙, 伊藤貴子, 宇留野晃, 中村美輝, 高橋 朗, 吉川雄朗, 清水恭子, 箱田明子, 工藤正孝, 伊藤貞嘉, 菅原 明
第85回日本内分泌学会学術総会, 19 Apr. 2012, Oral presentation
JAPAN 名古屋, [Domestic Conference]

高血糖刺激はアルドステロン合成酵素遺伝子（CYP11B2)の発現を増強する　　　　　　　　　　　　　　　
伊藤貴子, 松田謙, 宇留野晃, 清水恭子, 吉川雄朗, 工藤正孝, 箱田明子, 伊藤貞嘉, 菅原明
第23回間脳・下垂体・副腎系研究会, 31 Mar. 2012, Oral presentation
JAPAN, [Domestic Conference]

各アンジオテンシンII受容体拮抗薬（ARB）はアルドステロン合成酵素遺伝子（CYP11B2）発現に異なる影響を及ぼすに　　　　　　　　　　　　　　　
松田謙, 宇留野晃, 伊藤貴子, 清水恭子, 吉川雄朗, 工藤正孝, 佐藤文俊, 箱田明子, 伊藤貞嘉, 菅原明
第23回間脳・下垂体・副腎系研究会, 31 Mar. 2012, Oral presentation
JAPAN, [Domestic Conference]

種々のレチノイドX受容体（RXR）アゴニストは、AtT20細胞の増殖・アポトーシス・POMC発現・ACTH分泌に異なる影響を及ぼす　　　　　　　　　　　　　　　
箱田明子, 宇留野晃, 清水恭子, 伊藤貴子, 吉川雄朗, 藤原幾磨, 松田謙, 工藤正孝, 影近弘之, 岩崎泰正, 伊藤貞嘉, 菅原明
第23回間脳・下垂体・副腎系研究会, 31 Mar. 2012, Oral presentation
JAPAN, [Domestic Conference]

[18F]THK-523によるin vivoタウイメージング　　　　　　　　　　　　　　　
原田龍一, 岡村信行, 古本祥三, 吉川雄朗, 荒井啓行, 谷内一彦, 工藤幸司
第85回日本薬理学会年会, 14 Mar. 2012, Oral presentation
JAPAN 京都, [Domestic Conference]

ヒスタミン3型受容体による膵ß細胞機能の制御　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 野口直哉, 長沼史登, 原田龍一, Attayeb Mohsen, 飯田智光, 笠島敦子, 笹野公伸, 谷内一彦
第85回日本薬理学会年会, 14 Mar. 2012, Oral presentation
JAPAN 京都, [Domestic Conference]

正常ヒトアストロサイトによるヒスタミン取込はPMATを介して行われる　　　　　　　　　　　　　　　
吉川雄朗, 長沼史登, 中村正帆, 飯田智光, 谷内一彦
第85回日本薬理学会年会, 14 Mar. 2012, Oral presentation
JAPAN 京都, [Domestic Conference]

ヒトアストロサイトーマ由来細胞株はPMATを介してドパミンを取り込む　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 飯田智光, 谷内一彦
第85回日本薬理学会年会, 14 Mar. 2012, Poster presentation
JAPAN 京都, [Domestic Conference]

H3 receptor blockade increases locomotor activity in sleep-deprived wild type and H1 receptor knockout mice　　　　　　　　　　　　　　　
Attayeb Mohsen, 長沼史登, 渋谷勝彦, 中村正帆, 吉川雄朗, 岡村信行, 谷内一彦
第85回日本薬理学会年会, 14 Mar. 2012, Poster presentation
JAPAN 京都, [Domestic Conference]

Selective detection of tau neuropathology with novel fluorescent probes　　　　　　　　　　　　　　　
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Yukitsuka Kudo, Kazuhiko Yanai
第18回GCOE国際シンポジウム, 05 Mar. 2012, Poster presentation
仙台, [International presentation]

The expression and functions of histamine H3 receptor in pancreatic ß-cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Kazuhiko Yanai
第18回GCOE国際シンポジウム, 05 Mar. 2012, Poster presentation
仙台, [International presentation]

Wavelength-dependent detection of senile plaques and nuerofibrillary tangles with novel fluorescent probes　　　　　　　　　　　　　　　
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Yukitsuka Kudo, Kazuhiko Yanai
NRF-JSPS Asian Science Seminar, 13 Feb. 2012, Poster presentation
ソウル, [International presentation]

Histamine H3 recptor regulates the functions of pancreatic ß-cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Ryuichi Harada, Attayeb Mohsen, Masashi Saito, Kazuhiko Yanai
NRF-JSPS Asian Science Seminar, 13 Feb. 2012, Poster presentation
ソウル, [International presentation]

18F標識アミノ酸と無細胞蛋白質合成系を用いたポジトロン標識蛋白質の合成法の開発　　　　　　　　　　　　　　　
原田龍一, 古本祥三, 吉川雄朗, 石渡喜一, 岩田錬, 谷内一彦
第5回リトリート研究発表会, 21 Jan. 2012, Oral presentation
JAPAN 仙台, [Domestic Conference]

膵β細胞におけるヒスタミン3型受容体の発現とインスリン分泌での役割　　　　　　　　　　　　　　　
中村 正帆, 大杉 真也, 吉川 雄朗, 谷内 一彦
日本薬理学雑誌, Jan. 2012, (公社)日本薬理学会, Japanese
Jan. 2012 - Jan. 2012

ヒトアストロサイトによるヒスタミン取り込み機構　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 中村 正帆, 井筒 敏恵, 谷内 一彦
日本薬理学雑誌, Jan. 2012, (公社)日本薬理学会, Japanese
Jan. 2012 - Jan. 2012

Predominant role of PMAT in histamine uptake by normal human astrocytes　　　　　　　　　　　　　　　
Takeo Yoshikawa, Fumito Naganuma, Tadaho Nakamura, Tomomitsu Iida, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2012, JAPANESE PHARMACOLOGICAL SOC, English
2012 - 2012

A human astrocytoma-derived cell line transports dopamine through PMAT　　　　　　　　　　　　　　　
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2012, JAPANESE PHARMACOLOGICAL SOC, English
2012 - 2012

The expression and functions of histamine H3 receptor in pacreatic ß-cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Kazuhiko Yanai
5th east asian pacific student workshop on nano-biomedical engineering, 12 Dec. 2011, Poster presentation
[International presentation]

in vitro binding analysis of THK523 to Aß and tau protein fibirils　　　　　　　　　　　　　　　
R Harada, N Okamura, S Furumoto, T Yoshikawa, H Arai, Y Kudo, k Yanai
Neuroscience 2011, 12 Nov. 2011, Poster presentation
ワシントンDC, [International presentation]

インスリン分泌膵ß細胞におけるヒスタミン3型受容体の発現と機能　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 野口直哉, 大杉真也, 笠島敦子, 笹野公伸, 谷内一彦
第15回日本ヒスタミン学会, 21 Oct. 2011, Oral presentation
JAPAN 盛岡, [Domestic Conference]

正常ヒトアストロサイトによるヒスタミン取り込み機構の解明　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 井筒敏恵, 谷内一彦
第15回日本ヒスタミン学会, 21 Oct. 2011, Oral presentation
JAPAN 盛岡, [Domestic Conference]

Locomotor activity and antigenic-like behaviors are increased by histamine H3 receptors antagonist　　　　　　　　　　　　　　　
Attayeb, Mohsen, FUmito Naganuma, Tadaho Nakamura, Katsuhiko Shibuya, Takeo Yoshikawa, Nobuyuki Okamura, Kazuhiko Yanai
第15回日本ヒスタミン学会, 21 Oct. 2011, Oral presentation
JAPAN 盛岡, [Domestic Conference]

膵ß細胞におけるヒスタミン3型受容体の発現とインスリン分泌　　　　　　　　　　　　　　　
中村正帆, 大杉真也, 吉川雄朗, 谷内一彦
第62回日本薬理学会北部会, 29 Sep. 2011, Oral presentation
JAPAN 仙台, [Domestic Conference]

ヒトアストロサイトによるヒスタミン取り込み機構　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 井筒敏恵, 谷内一彦
第62回日本薬理学会北部会, 29 Sep. 2011, Oral presentation
JAPAN 仙台, [Domestic Conference]

Histamine H3 receptors antagonists increase anziogenic-like behaviors and locomotor activity　　　　　　　　　　　　　　　
A Mohsen, F Naganuma, T Nakamura, T Yoshikawa, N Okamura, K Yanai
第62回日本薬理学会北部会, 29 Sep. 2011, Oral presentation
JAPAN 仙台, [Domestic Conference]

Important role of plasma membrane monoamine transporters in histamine uptake by human astrocytes　　　　　　　　　　　　　　　
F Naganuma, T Yoshikawa, T Nakamura, T Idutsu, K Yanai
第54回日本神経化学学会, 26 Sep. 2011, Oral presentation
JAPAN 金沢, [Domestic Conference]

膵ß細胞に発現しているヒスタミン3型受容体はブドウ糖刺激インスリン分泌を抑制する　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 大杉真也, 長沼史登, 野口直哉, 谷内一彦
第84回日本生化学会大会, 21 Sep. 2011, Oral presentation
JAPAN 京都, [Domestic Conference]

in vitro comparative binding studies: amyloid and tau imaging probes　　　　　　　　　　　　　　　
原田龍一, 岡村信行, 古本祥三, 吉川雄朗, 荒井啓行, 工藤幸司, 谷内一彦
第34回日本神経科学会年回, 14 Sep. 2011, Oral presentation
JAPAN 横浜, [Domestic Conference]

The mechanism of histamine uptake by human astrocytoma-derived cell line　　　　　　　　　　　　　　　
F Naganuma, T Yoshikawa, T Nakamura, T Idutsu, K Yanai
第34回日本神経科学会年会, 14 Sep. 2011, Oral presentation
JAPAN 横浜, [Domestic Conference]

膵β細胞に発現しているヒスタミン3型受容体はブドウ糖刺激インスリン分泌を抑制する　　　　　　　　　　　　　　　
中村 正帆, 吉川 雄朗, 大杉 真也, 長沼 史登, 野口 直哉, 谷内 一彦
日本生化学会大会プログラム・講演要旨集, Sep. 2011, (公社)日本生化学会, Japanese
Sep. 2011 - Sep. 2011

ヒトアストロサイトによるヒスタミン取り込み機構について(Important role of plasma membrane monoamine transporters in histamine uptake by human astrocytes)　　　　　　　　　　　　　　　
長沼 史登, 吉川 雄朗, 中村 正帆, 井筒 敏恵, 谷内 一彦
神経化学, Sep. 2011, 日本神経化学会, English
Sep. 2011 - Sep. 2011

Histamine receptor H3 regulates the functions of pancreatic ß-cells　　　　　　　　　　　　　　　
T Nakamura, T Yoshikawa, N Noguchi, H Okamoto, A Sugawara, K Yanai
America Diabetes Association, 71th sicentific sessions, 24 Jun. 2011, Poster presentation
サンディエゴ, [International presentation]

The role of histamine receptro H3 in pancreatic ß-cells　　　　　　　　　　　　　　　
T Nakamura, T Yoshikawa, N Noguchi, M Ohsugi, K Yanai
The 40th anniversary European Histamine Resarch Society meeting, 11 May 2011, Oral presentation
ソチ, [International presentation]

ヒスタミン3型受容体による膵β細胞機能の制御　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 野口直哉, 大杉真也, 谷内一彦
糖尿病, Apr. 2011, Japanese
Apr. 2011 - Apr. 2011

The role of histamine H3 receptor in pancreatic β-cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Naoya Noguchi, Kazuhiko Yanai
第８４回日本薬理学会年会, 22 Mar. 2011, Oral presentation
JAPAN 横浜, [Domestic Conference]

Repeated exposeres to the elevated zero maze increase anxiety in mice: gender difference　　　　　　　　　　　　　　　
Attayeb Mofsen, Tadaho Nakamura, Fumito Naganuma, Takeo Yoshikawa, Zhang Dongying, Nobuyuki Okamura, Kazuhiko Yanai
第８４回日本薬理学会年会, 22 Mar. 2011, Poster presentation
JAPAN 横浜, [Domestic Conference]

Potential ce3ntral sedative effect of antihistamine eye-drops: histamine H1 receptor occupancy measured by positron emission tomography　　　　　　　　　　　　　　　
Dongying Zhang, Katsuhiko Shibuya, manabu Tashiro, Ryuichi Harada, Takeo Yoshikawa, Nobuyuki Okamura, Kazuhiko Yanai
第８４回日本薬理学会年会, 22 Mar. 2011, Poster presentation
JAPAN 横浜, [Domestic Conference]

The deficiency of histamine h3 receptor increases the sensitiviy of morphine-induced hyperlocomotion without affecting the reward in mice　　　　　　　　　　　　　　　
Dongying Zhang, Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Attayeb Mofsen, Kazuhiko Yanai
第８４回日本薬理学会年会, 22 Mar. 2011, Poster presentation
JAPAN 横浜, [Domestic Conference]

ヒトアストロサイトーマ由来細胞株におけるヒスタミン取り込み機構　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 井筒敏恵, 中村正帆, 谷内一彦
第８４回日本薬理学会年会, 22 Mar. 2011, Poster presentation
JAPAN 横浜, [Domestic Conference]

膵β細胞機能におけるヒスタミン３型受容体の機能解析　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 谷内一彦
第４回リトリート大学院生研究発表会, 15 Jan. 2011, Poster presentation
JAPAN 仙台, [Domestic Conference]

アストロサイトによるヒスタミン取り込み機構の解明　　　　　　　　　　　　　　　
長沼史登, 吉川雄朗, 中村正帆, 井筒敏恵, 谷内一彦
第４回リトリート大学院生研究発表会, 15 Jan. 2011, Poster presentation
JAPAN 仙台, [Domestic Conference]

In vitro comparative binding studies: Amyloid and tau imaging probes
Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Hiroyuki Arai, Yukitsuka Kudo, Kazuhiko Yanai
NEUROSCIENCE RESEARCH, 2011, ELSEVIER IRELAND LTD, English
2011 - 2011

Potential central sedative effect of antihistamine eye-drops: histamine H-1 receptor occupancy measured by positron emission tomography　　　　　　　　　　　　　　　
Dongying Zhang, Katsuhiko Shibuya, Manabu Tashiro, Ryuichi Harada, Nobuyuki Okamura, Takeo Yoshikawa, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2011, JAPANESE PHARMACOLOGICAL SOC, English
2011 - 2011

Repeated exposures to the elevated zero maze increase anxiety in mice: gender difference　　　　　　　　　　　　　　　
Attayeb Mohsen, Tadaho Nakamura, Fumito Naganuma, Takeo Yoshikawa, Dongying Zhang, Nobuyuki Okamura, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2011, JAPANESE PHARMACOLOGICAL SOC, English
2011 - 2011

The molecular mechanism of histamine uptake by human astrocytoma-derived cell line
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Toshie Idutsu, Kazuhiko Yanai
NEUROSCIENCE RESEARCH, 2011, ELSEVIER IRELAND LTD, English
2011 - 2011

The deficiency of histamine H3 receptor increases the sensitivity of morphine-induced hyperlocomotion without affecting the reward in mice　　　　　　　　　　　　　　　
Dongying Zhang, Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Attayeb Mohsen, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2011, JAPANESE PHARMACOLOGICAL SOC, English
2011 - 2011

Histamine clearance in human astrocytoma derived cell lines　　　　　　　　　　　　　　　
Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Toshie Idutsu, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2011, JAPANESE PHARMACOLOGICAL SOC, English
2011 - 2011

The role of histamine H3 receptor in pancreatic beta-cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Naoya Noguchi, Kazuhiko Yanai
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2011, JAPANESE PHARMACOLOGICAL SOC, English
2011 - 2011

Histamine receptor H3 regulates insulin secretion in mouse pancreatic β-cell line MIN6 cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Junya Fukuda, Naoya Noguchi, Kazuhiko Yanai
4th east asian pacific student workshop on nano-biomedical engineering, 15 Dec. 2010, Poster presentation
Singapore Singapore, [International presentation]

The role of histamine H3 receptro in the functions of pancreatic β-cells　　　　　　　　　　　　　　　
中村正帆, 吉川雄朗, 野口直哉, 谷内一彦
第３３回日本分子生物学会・第８３回日本生化学会大会 合同大会, 07 Dec. 2010, Poster presentation
JAPAN 神戸, [Domestic Conference]

Histamine-H3R-deficiency increased the sensitivity of morphine-induced hyperactivity but unaffected the rewarding response in in mice　　　　　　　　　　　　　　　
張冬穎, 吉川雄朗, 長沼史登, 中村正帆, 岡村信行, 加藤正人, 谷内一彦
第61回日本薬理学会北部会, 10 Sep. 2010, Oral presentation
JAPAN 札幌, [Domestic Conference]

内標準法によるヒスタミンと1-メチルヒスタミンの同時測定　　　　　　　　　　　　　　　
長沼史登, 井筒敏恵, 張冬穎, 中村正帆, 原田龍一, 吉川雄朗, 岡村信行, 谷内一彦
第61回日本薬理学会北部会, 10 Sep. 2010, Oral presentation
JAPAN 札幌, [Domestic Conference]

Histamine receptors and stress vulnerability　　　　　　　　　　　　　　　
谷内一彦, 吉川雄朗, 櫻井映子, 及川綾子, 長沼史登, 岡村信行
第33回日本神経化学大会, 02 Sep. 2010, Poster presentation
JAPAN 神戸, [Domestic Conference]

Histamine Receptor H3 Regulates Insulin Secretion in Mouse Pancreatic β-cell Line MIN6 cells　　　　　　　　　　　　　　　
Tadaho Nakamura, Takeo Yoshikawa, Junya Fukuda, Naoya Noguchi, Kazuhiko Yanai
KIST-Tohoku Joint Symposium on Nanobiomedical Engineering, 30 Aug. 2010, Poster presentation
Republic of Korea ソウル, [International presentation]

ole of heparan sulfate in glucose-induced insulin secretion in mouse pancreatic β-cell line MIN6 cells　　　　　　　　　　　　　　　
Takeo Yoshikawa, S Takayanagi, N Noguchi, D Zhang, Y Ariyama, A Uruno, H Okamoto, A Sugawara, K Yanai
16th world congress of basic and clinical pharmacology, 17 Jul. 2010, Poster presentation
Denmark コペンハーゲン, [International presentation]

Molecular imaging in Alzheimer's disease: from basic to clinical　　　　　　　　　　　　　　　
K Yanai, S Furumoto, T Yoshikawa, R Iwata, M Tashiro, N Okamura
16th world congress on basic and clinical pharmacology, 17 Jul. 2010, Oral presentation
Denmark コペンハーゲン, [International presentation]

Role of Heparan Sulfate in Glucose-Induced Insulin Secretion in MIN6 Cells　　　　　　　　　　　　　　　
Takeo Yoshikawa, Shiori Takayanagi, Naoya Noguchi, Akira Uruno, Hiroshi, Okamoto, Akira Sugawara, Kazuhiko Yanai
the American Diabetes Association's 70th Scientific Sessions., 25 Jun. 2010, Poster presentation
United States Orland, FL, [International presentation]

PPARgamma down-regulates CYP11B2 expression and aldosterone production in adrenocortical carcinoma H295R cells by suppression of Ca2+-CaMK signals　　　　　　　　　　　　　　　
Akira Uruno, Ken Matsuda, Naoya Noguchi, Takeo Yoshikawa, Masataka Kudo, Fumitoshi Satoh, William E. Rainey, Hiroshi Okamoto, Sadayoshi Ito, Akira Sugawara
International symposium for aldosterone and related substances in hypertension, 24 Mar. 2010, Oral presentation
JAPAN 仙台, [International presentation]

新規開発HPLC法を用いたヒスタミン代謝についての検討　　　　　　　　　　　　　　　
井筒敏恵, 櫻井映子, 及川綾子, 高柳詩織, 吉川雄朗, 谷内一彦
第53回日本薬理学会年会, 16 Mar. 2010, Poster presentation
JAPAN 大阪, [Domestic Conference]

ストレス条件下でのヒスタミン受容体の応答と役割ーヒスタミン受容体欠損マウスをもちいて　　　　　　　　　　　　　　　
及川綾子, 櫻井映子, 井筒敏恵, 張冬穎, 助川淳, 吉川雄朗, 谷内一彦
第39回日本精神神経薬理学会年会, 13 Nov. 2009, Poster presentation
JAPAN, [Domestic Conference]

PPARgammaはCaＭＫ-ATF-2のシグナル伝達を抑制し、アンジオテンシン？/カリウム応答性アルドステロン分泌を抑制する　　　　　　　　　　　　　　　
宇留野晃, 松田謙, 野口直哉, 工藤正孝, 佐藤文俊, 伊藤貞嘉, 岡本宏, 菅原明
第13回日本心血管内分泌代謝学会学術総会, 23 Oct. 2009, Poster presentation
JAPAN 大宮, [Domestic Conference]

2型リアノジン受容体遺伝子にはGG-AG配列で切断されるイントロンが存在する　　　　　　　　　　　　　　　
池田崇之, 野口直哉, 吉川雄朗, 宇留野晃, 那谷耕司, 高沢伸, 岡本宏, 米倉秀人, 菅原明
第82回日本生化学会大会, 21 Oct. 2009, Oral presentation
JAPAN 神戸, [Domestic Conference]

Sera from Japanese diabetes patients show autoimmunity to REG family antigens　　　　　　　　　　　　　　　
NJ. Shervani, K. Nata, N. Noguchi, I. Takahashi, T. Ikeda, K. Ohashi, T. Yoshikawa, A. Uruno, S. Takasawa, H. Okamoto, A. Sugawara
第82回日本生化学会大会, 21 Oct. 2009, Poster presentation
JAPAN 神戸, [Domestic Conference]

ブドウ糖刺激インスリン分泌におけるFKBP12.6結合たんぱく質12.6の関与　　　　　　　　　　　　　　　
吉川雄朗, 野口直哉, 高柳詩織, 張冬頴, 有山雄太, 宇留野晃, 菅原明, 谷内一彦
第37回薬物活性シンポジウム, 09 Oct. 2009, Oral presentation
JAPAN 仙台, [Domestic Conference]

ストレス反応に対するヒスタミン受容体の応答変化　　　　　　　　　　　　　　　
及川綾子, 櫻井映子, 井筒敏恵, 張冬穎娃, 助川淳, 吉川雄朗, 谷内一彦
第13回日本ヒスタミン学会, 08 Oct. 2009, Oral presentation
JAPAN 仙台, [Domestic Conference]

Autoantibodies to REG family proteins in Japanese diabetes patients　　　　　　　　　　　　　　　
NJ. Shervani, N. Noguchi, T. Ikeda, I. Takahashi, T. Yoshikawa, A. Yamauchi, A. Uruno, K. Nata, S. Takasawa, H. Okamoto, A. Sugawara
European Association for the Study of Diabetes, 29 Sep. 2009, Poster presentation
Austria Vienna, [International presentation]

FK506結合蛋白質12.6ノックアウトマウスではブドウ糖刺激インスリン分泌が低下する　　　　　　　　　　　　　　　
吉川雄朗, 野口直哉, 高柳詩織, 宇留野晃, 菅原明, 谷内一彦
第60回日本薬理学会北部会, 26 Sep. 2009, Oral presentation
JAPAN 富山, [Domestic Conference]

ヒスタミン代謝物とヒスタミンの同時測定：培養細胞への応用　　　　　　　　　　　　　　　
井筒敏恵, 櫻井映子, 及川綾子, 吉川雄朗, 谷内一彦
第60回日本薬理学会北部会, 26 Sep. 2009, Oral presentation
JAPAN 富山, [Domestic Conference]

PPARgamma suppresses antiotensin II- and potassium-induced CYP11B2 expression and aldosterone pruduction in adrenocortical carcinoma H295 cells　　　　　　　　　　　　　　　
A. Uruno, K. Matsuda, N. Noguchi, T. Yoshikawa, M. Kudo, F. Satoh, WE. Rainey, S. Ito, H. Okamoto, A. Sugawara
35th meeting of the International Aldosterone Conference, 08 Jun. 2009, Poster presentation
United States Washington, [International presentation]

マウス膵β細胞におけるヘパラン硫酸とインスリン分泌の維持　　　　　　　　　　　　　　　
野口直哉, 高橋巌, 吉川雄朗, NJ Shervani, 宇留野晃, 海野倫明, 岡本宏, 菅原明
第52回日本糖尿病学会年次学術集会, 21 May 2009, Poster presentation
JAPAN 大阪, [Domestic Conference]

Predominant role of REGIα among the REG gene family in the proliferation of human colorectal adenocarcinoma　　　　　　　　　　　　　　　
T. Yoshikawa, T. Ikeda, K. Sakai, N. Noguchi, I. Takahashi, NJ. Shervani, A Uruno, A. Yamauchi, E. Sakai, T. Onogawa, M. Okabe, T. Ando, M. Kinouchi, K. Miura, M. Unno, T. Emura, M. Fujiwara, S. Takasawa, H. Okamoto, A. Sugawara
American Association for Cancer Research, 18 Apr. 2009, Poster presentation
United States デンバー, [International presentation]

消化器癌における全REG遺伝子の発現解析および増殖効果の検討　　　　　　　　　　　　　　　
吉川雄朗, 池田崇之, 坂井和子, 野口直哉, 高橋巌, NJ Shervani, 宇留野晃, 山内晶世, 酒井栄一, 小野川徹, 渋谷恵美子, 岡部光規, 安藤敏典, 木内誠, 三浦康, 海野倫明, 江村智博
第31回日本分子生物学会年会・第81回日本生化学会大会合同大会, 09 Dec. 2008, Poster presentation
JAPAN 神戸, [Domestic Conference]

Reduced beta cell proliferation and impaired glucose tolerance in pancreatic betra cell specific Extl3 knockout mice　　　　　　　　　　　　　　　
I. Takahashi, K. Nata, N. Noguchi, T. Ikeda, K. Sugihara, M. Asano, T. Yoshikawa, NJ. Shervani, A. Uruno, M. Unno, S. Takasawa, H. Okamoto, A. Sugawara
The 44th European Association for the Study of Diabetes, 07 Sep. 2008, Poster presentation
Italy Roma, [International presentation]

Impaired glucose-induced insulin secretion in FK506-binding protein 12.6-deficient mice　　　　　　　　　　　　　　　
T. Yoshikawa, N. Noguchi, T. Ikeda, I. Takahashi, NJ. Shervani, A. Uruno, Y. Yamauchi, K. Nata, S. Takasawa, H. Okamoto, A. Sugawara
American Diabetes Association's 68th Scientific Sessions, 06 Jun. 2008, Oral presentation
United States San Francisco, [International presentation]

FK506結合蛋白質１２．６ノックアウトマウスにおけるグルコース刺激インスリン分泌の低下　　　　　　　　　　　　　　　
吉川雄朗, 野口直哉, 池田崇之, 高橋巌, NJ Shervani, 宇留野晃, 山内晶世, 那谷耕司, 高沢伸, 岡本宏, 菅原明
第51回日本糖尿病学会年次学術集会, 22 May 2008, Oral presentation
JAPAN 東京, [Domestic Conference]

膵β細胞特異的糖転移酵素EXTL３欠損マウスはβ細胞増殖能低下と耐糖能異常を生じる　　　　　　　　　　　　　　　
高橋巌, 那谷耕司, 野口直哉, 池田崇之, 吉川雄朗, 山内晶世, NJ Shervani, 宇留野晃, 杉原一司, 浅野雅秀, 海野倫明, 高沢伸, 岡本宏, 菅原明
第51回日本糖尿病学会年次学術集会, 22 May 2008, Oral presentation
JAPAN 東京, [Domestic Conference]

中枢神経系脆弱性と全身麻酔に関連した周術期認知機能障害の神経病理解析
科学研究費助成事業
01 Apr. 2023 - 31 Mar. 2027
中村 正帆, 吉川 雄朗, 長沼 史登
日本学術振興会, 基盤研究(C), 東北医科薬科大学, 23K08342

Elucidation of important research issues to be solved in pharmacological research on histamine
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2025
谷内 一彦, 吉川 雄朗, 中村 正帆
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tohoku University, 22H02808

Analysis of heparanse in skeletal muscles
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2021 - 31 Mar. 2024
吉川 雄朗, 有澤 美枝子
ヘパラン硫酸は細胞外に豊富に存在する直鎖状糖鎖の一つである。これまでに我々が実施した研究によりヘパラン硫酸は骨格筋に発現していること、骨格筋でヘパラン硫酸を欠損させると、正常な筋分化が阻害され、運動機能が低下することが示されている。そこで骨格筋においてヘパラン硫酸を増加させることは、筋分化を促進し、運動機能を改善する可能性が考えられた。そこで骨格筋に限定してヘパラン硫酸を増加させた場合に、骨格筋機能にどのような変化が生じるかを検討することとした。ヘパラン硫酸を増加させるために、まずヘパラン硫酸分解酵素に着目した。ヘパラン硫酸分解酵素（heparan sulfate endoglycosidase、HPSE）を抑制することで、ヘパラン硫酸量が増加すると考えられるため、ヘパラン硫酸分解酵素のfloxマウス（HPSE floxマウス）を新規に導入した。また骨格筋特異的にHPSE機能を欠損させるため、HPSE floxマウスと骨格筋特異的にCre recombinaseを発現するCKMM-Creマウスとを交配させ、これまでにヘテロ欠損マウスを得ている。今後骨格筋特異的にHPSEをホモ欠損したマウスを得て、表現型解析を実施する。また阻害剤の探索研究に必要なHPSEを得るために、293細胞にHPSEを安定発現させた細胞株を樹立した。HPSEにはタグを付与しており、このタグを用いることで純度の高いHPSEを得る。その後精製したHPSEを用いて酵素活性確認とハイスループットスクリーニング系の構築を実施する。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tohoku University, 21K06795

吸入麻酔薬の意識消失作用におけるニューロテンシン神経系の役割
科学研究費助成事業 基盤研究(C)
01 Apr. 2020 - 31 Mar. 2023
中村 正帆, 吉川 雄朗, 長沼 史登
睡眠から覚醒への移行に関わる覚醒系神経回路は、ヒスタミン神経細胞などのモノアミン神経系とそれを制御するオレキシン神経細胞などの神経ペプチド系により構成されている。これらの神経細胞が活性化することが、覚醒への移行と維持に重要であると考えられている。吸入麻酔薬の意識消失作用は、これらの神経細胞や神経回路を抑制することで発揮されると仮説し、以下の実験を行い（あるいは現在行っている）、以下の結果が得られた（あるいはデータ取得の途中である）。
１）神経ペプチド系のニューロテンシン神経細胞とモノアミン神経系のヒスタミン神経細胞の活性化が、吸入麻酔薬によってどのように変化するかを、生体内の神経細胞活動を測定するファイバーフォトメトリーを用いて検討した。原則として吸入麻酔薬はニューロテンシン神経細胞とヒスタミン神経細胞の細胞活性を抑制した（する傾向を示した）が、吸入麻酔薬の種類や濃度によって一様に抑制されるわけではないことが明らかになった。対象神経細胞の局在によって細胞活性の反応が異なる場合と、同じ局在の神経細胞でも反応が異なる場合があり、局在と神経細胞のサブポピュレーションについて精査する必要がある。２）薬理遺伝学的手法を用いて対象神経細胞を特異的に活性化あるいは不活性化した時に、吸入麻酔薬の意識消失作用がどのように変化するかを検討した。対象神経細胞を特異的に活性化すると吸入麻酔薬が作用しづらくなり（用量反応曲線が右方にシフトする）、不活性化した場合は左方にシフトする傾向を示した。
日本学術振興会, 基盤研究(C), 東北医科薬科大学, 20K09204

Translational research of a 18F-labeled cation type myocardium perfusion imaging agent
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2019 - 31 Mar. 2022
Furumoto Shozo
Translational research is needed to apply the PET agents developed in basic research to clinical research, which involves establishing a system to produce high-quality PET agents for routine clinical use. In this study, we aimed to establish a reliable method to produce 18F-TAP-X PET agents for clinical use, which we developed for myocardial blood flow imaging, by using a globally available commercial radiolabeling synthesizer. We were able to purify 18F-TAP-X to high purity in this study using only solid-phase extraction column cartridges without HPLC purification. Then, we succeeded in producing an 18F-TAP-X solution available as an injection agent by FASTlab, leading the way to its clinical application.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tohoku University, 19H03595

Mechanism of histamine-induced aggresive behaviors in mice
Grants-in-Aid for Scientific Research
01 Apr. 2018 - 31 Mar. 2021
Yoshikawa Takeo
I evaluated the involvement of histaminergic nervous system in aggressive behaviors in mice. Brain histamine exerts its effect through the regulation of neuron or astrocytes functions. Thus, we investigated the importance of neuronal or astrocytic histamine H1 receptor in aggressive behaviors. Astrocyte-specific deletion of H1 receptor resulted in the increase of attack number in resident-intruder tests, indicating the importance of astrocytes for aggressive behaviors. Next, we used DREADDs (designer receptor exclusively activated by designer drugs) technology to examine the impact of acute histaminergic activation or inhibition on aggression. Acute histaminergic activation led to the enhanced aggressive behaviors. These results confirm the importance of histaminergic nervous system for the regulation of aggressive behaviors.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tohoku University, 18K06886

Development of a novel labeling method for affibody by F-18 labeled amino acid and a cell-free protein synthesis system
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2016 - 31 Mar. 2018
Yanai Kazuhiko
In this study, we tried to develop a novel labeling method for affibody molecular that possess high binding affinity to targets and fast pharmacokinetics by F-18 labeled amino acid and a cell-free protein synthesis system. 18F-O-2-fluoroethyl tyrosine (FET) was successfully incorporated into proteins by using commercially available cell-free protein synthesis reagents with an engineered aminoacyl transferase/ tRNACUAopt pair and template DNA of the desired proteins inserted with an amber codon. 18F-labeled affibody for human epidermal growth factor receptor type 2 (HER2) demonstrated that high binding to SKOV-3 expressing HER2 with high level. In vivo PET imaging in SKOV-3 xenograft-bearing mice showed that high tracer accumulation in the SKOV-3 xenografts. In conclusion, this method might be useful for preparation of proteins with F-18 and molecular imaging in preclinical development.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Tohoku University, 16K15314

Importance of histamine metabolizing enzyme in the brain
Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
01 Apr. 2016 - 31 Mar. 2018
Yoshikawa Takeo
HIstamine acts as a neurotransmitter in the central nervous system. In this study,I examined the importance of a histamine metabolizing enzyme for brain functions. I revealed the essential role of this enzyme in the regulation of brain histamine and the contribution to brain functions such as sleep-wake cycle and aggression. Previous reports showed that brain histamine concentration was decreased in various brain diseases. Thus, I tried to develop new inhibitors against the histamine metabolizing enzyme to increase brain histamine concentration. I have confirmed that several compounds have sufficient inhibitory effects on the histamine metabolizing enzyme.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Tohoku University, 16K18389

Analysis of histamine system through genetically modified mice
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
27 Jun. 2014 - 31 Mar. 2018
Yanai Kazuhiko
We investigated the role of brain histamine. We examined the importance of histamine N-methyltransfease (HNMT) for brain functions. Our results showed the essential role of HNMT in the regulation of brain histamine concentration. The aggression and sleep-wake cycles are also controlled by HNMT. We also investigated the involvement of histamine in glial cell functions. Histamine activated astrocytes through histamine H1 receptors. Histamine H3 receptor antagonists improved depression-like behaviors by the modulation of microglial activity. These results demonstrated the importance of histamine clearance for brain functions and the contribution of histamine to glial activity.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Tohoku University, 26253016

Analysis of plasma membrane monoamine transporter in brain
Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
01 Apr. 2014 - 31 Mar. 2016
Yoshikawa Takeo
Plasma membrane monoamine transporter (PMAT) is one of the monoamine transporters in brain. However, the role of PMAT in the regulation of monoamine concentration remains to be elucidated. In the present study, we generated PMAT-deficient mice, but analysis of PMAT-deficient mice is now on going. We also try to develop specific inhibitors against PMAT. We performed high-throughput screening to get PMAT specific inhibitors and got some candidate compounds until now.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Tohoku University, 26830041

Molecular mechanism of brain histamine clearance
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2014 - 31 Mar. 2015
YANAI Kazuhiko, WATANABE Takehiko, YOSHIKAWA Takeo
Histamine plays an important role in brain functions such as sleep-wake cycle and stress response. We investigated the molecular mechanism of histamine clearance. We demonstrated that histamine N-methyltransferase, which inactivates histamine, was one of the essential factors for histamine clearance.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Tohoku University, 26670117

Generation of molecular imaging pharmacology using small primate mamosets
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2012 - 31 Mar. 2014
YANAI KAZUHIKO, YOSHIKAWA Takeo, SHIBUYA Katsuhiko
The marmoset animals are very useful for translational research. In order to keep marmosets in the PET facility and use the animals for small animal PET imaging, we investigated the regulations on animal breeding in the restricted areas of short half-life radioisotopes. We recognized that the animals administered with carbon-11 (half-life 20 min) and fluorine-18 (half-life 110 min) should be kept inside the PET centers for one week. In parallel, we performed molecular imaging studies on small animals. It is possible to estimate the radiation dosimetry in humans from distribution data obtained by small animal PET. The advantage of molecular imaging is reduction of used animals for translational research.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Tohoku University, 24659255

Integrated research of histamine system from molecular to wholeanimals and humans using leading-edge technologies
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2009 - 2011
YANAI Kazuhiko, WATANABE Takehiko, YOSHIKAWA Takeo, KURAMASU Atsuo, SAKURAI Eiko, OKAMURA Nobuyuki
Using leading-edge te chnologies, this study examined new roles of neuronal histamine which have not been fully dissolved. This study was performed on the experiments of molecular and cellular levels and whole animals, and we attempted the results were directly connected to tra nslational human PET studies. Main findings of this study are as follows : 1)The role of C-terminal on H3 receptors-mediated signal transduction were clarified ; 2)The transport of histamine in the CNS was mediated through a newly-identified non-specific t ransporter, PMAT (plasma membrane monoamine transporter)in astrocytes. 3)The existence and roles of H3 receptors in pancreatic islet cells were discovered for the first time. 4)The roles of histamine receptors on whole animals' behavioral levels were ex amined using histamine receptors knockout mice. 5)Brain pharmacokinetics of antihistamines was revealed using molecular PET imaging on the term of H1 receptor occupancy.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tohoku University, 21390171