Researcher basic information

• 博士（獣医学）, 北海道大学

• https://researchmap.jp/read0103117?lang=en

• https://orcid.org/0000-0002-2481-5592
• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200901054957273972
• http://www.vetmed.hokudai.ac.jp/organization/pharmacol/index.html

• 40344494

• https://orcid.org/0000-0002-2481-5592

• 200901054957273972

• アデノシン
• プリン受容体
• アストロサイト
• アドレナリン受容体
• 薬理学
• Cell biology
• Pharmacology

• Life Science, Veterinary medical science

• Bachelor's degree program, School of Veterinary Medicine
• Doctoral (PhD) degree program, Graduate School of Veterinary Medicine

Research activity information

• Epidermal growth factor increases cystathionine β-synthase expression in cultured embryonic spinal cord cells.
  Ryota Eguchi; Yuya Higashida; Mizuki Oouchi; Soichiro Yamaguchi; Ken-Ichi Otsuguro
  In vitro cellular & developmental biology. Animal, 61, 4, 416, 424, Apr. 2025, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, In the central nervous system (CNS), cystathionine β-synthase (CBS) is localized in astrocytes. CBS degrades cytotoxic homocysteine and produces cytoprotective hydrogen sulfide; thus the proper expression of CBS is required to maintain CNS functions. CBS expression is very low at the late embryonic stage and increases after birth. This study examined CBS expression in cultured spinal cord cells derived from fetal rats. Treatment of spinal cord cells with epidermal growth factor (EGF) promoted the proliferation and maturation of astrocytes during development. EGF (30 ng/ml, 4 days) increased CBS protein expression and the number of CBS-expressing astrocytes in the culture. A high cell density also increased CBS expression, and EGF was able to increase CBS expression when cellular proliferation was inhibited. The EGF receptor was predominately expressed in neural stem cells rather than astrocytes. These results suggest that EGF acts on neural stem cells, leading to increase in CBS-expressing astrocytes. This effect may reflect the maturation process of astrocytes during embryonic development.
• Short-term memory impairment following recovery from systemic inflammation induced by lipopolysaccharide in mice
  Kohei Morimoto; Shu Watanuki; Ryota Eguchi; Taisuke Kitano; Ken-ichi Otsuguro
  Frontiers in Neuroscience, 17, Frontiers Media SA, 18 Oct. 2023, [Peer-reviewed], [Last author, Corresponding author]
  Scientific journal, The relationship between neuroinflammation and mental disorders has been recognized and investigated for over 30 years. Diseases of systemic or peripheral inflammation, such as sepsis, peritonitis, and infection, are associated with increased risk of mental disorders with neuroinflammation. To elucidate the pathogenesis, systemic administration of lipopolysaccharide (LPS) in mice is often used. LPS-injected mice exhibit behavioral abnormalities with glial activation. However, these studies are unlikely to recapitulate the clinical pathophysiology of human patients, as most studies focus on the acute inflammatory response with systemic symptoms occurring within 24 h of LPS injection. In this study, we focus on the effects of LPS on behavioral abnormalities following recovery from systemic symptoms and investigate the mechanisms of pathogenesis. Several behavioral tests were performed in LPS-injected mice, and to assess neuroinflammation, the time course of the morphological change and expression of inflammatory factors in neurons, astrocytes, and microglia were investigated. At 7 days post-LPS injection, mice exhibited short-term memory impairment accompanied by the suppression of neuronal activity and increases in morphologically immature spines. Glial cells were transiently activated in the hippocampus concomitant with upregulation of the microglial phagocytosis marker CD68 3 days after injection. Here we show that transient glial cell activation in the acute response phase affects neuronal activity and behavior following recovery from systemic symptoms. These findings provide novel insights for studies using the LPS-induced inflammation model and that will contribute to the development of treatments for mental disorders of this etiology.
• The cytosolic N-terminal region of heterologously-expressed transmembrane channel-like protein 1 (TMC1) can be cleaved in HEK293 cells.
  Soichiro Yamaguchi; Maho Kamino; Maho Hamamura; Ken-Ichi Otsuguro
  PloS one, 18, 6, e0287249, 2023, [Peer-reviewed], [Last author], [International Magazine]
  English, Scientific journal, Transmembrane channel-like protein 1 (TMC1) is a transmembrane protein forming mechano-electrical transduction (MET) channel, which transduces mechanical stimuli into electrical signals at the top of stereocilia of hair cells in the inner ear. As an unexpected phenomenon, we found that the cytosolic N-terminal (Nt) region of heterologously-expressed mouse TMC1 (mTMC1) was localized in nuclei of a small population of the transfected HEK293 cells. This raised the possibility that the Nt region of heterologously-expressed mTMC1 was cleaved and transported into the nucleus. To confirm the cleavage, we performed western blot analyses. The results revealed that at least a fragment of the Nt region was produced from heterologously-expressed mTMC1. Site-directed mutagenesis experiments identified amino acid residues which were required to produce the fragment. The accumulation of the heterologously-expressed Nt fragment into the nuclei depended on nuclear localization signals within the Nt region. Furthermore, a structural comparison showed a similarity between the Nt region of mTMC1 and basic region leucine zipper (bZIP) transcription factors. However, transcriptome analyses using a next-generation sequencer showed that the heterologously-expression of the Nt fragment of mTMC1 hardly altered expression levels of genes. Although it is still unknown what is the precise mechanism and the physiological significance of this cleavage, these results showed that the cytosolic Nt region of heterologously-expressed mTMC1 could be cleaved in HEK293 cells. Therefore, it should be taken into account that the cleavage of Nt region might influence the functional analysis of TMC1 by the heterologous-expression system using HEK293 cells.
• Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors.
  Kohei Morimoto; Mai Ouchi; Taisuke Kitano; Ryota Eguchi; Ken-Ichi Otsuguro
  European journal of pharmacology, 928, 175110, 20 Jun. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 μM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 μM) were inhibited by a β-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 μM) promoted process formation, which was inhibited by a β-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and β-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and β-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and β-adrenoceptors were negatively regulated by D2-like receptors and α2-adrenoceptors.
• Glu333 in rabies virus glycoprotein is involved in virus attenuation through astrocyte infection and interferon responses.
  Yukari Itakura; Koshiro Tabata; Kohei Morimoto; Naoto Ito; Herman M Chambaro; Ryota Eguchi; Ken-Ichi Otsuguro; William W Hall; Yasuko Orba; Hirofumi Sawa; Michihito Sasaki
  iScience, 25, 4, 104122, 104122, 15 Apr. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, The amino acid residue at position 333 of the rabies virus (RABV) glycoprotein (G333) is a major determinant of RABV pathogenicity. Virulent RABV strains possess Arg333, whereas the attenuated strain HEP-Flury (HEP) possesses Glu333. To investigate the potential attenuation mechanism dependent on a single amino acid at G333, comparative analysis was performed between HEP and HEP333R mutant with Arg333. We examined their respective tropism for astrocytes and the subsequent immune responses in astrocytes. Virus replication and subsequent interferon (IFN) responses in astrocytes infected with HEP were increased compared with HEP333R both in vitro and in vivo. Furthermore, involvement of IFN in the avirulency of HEP was demonstrated in IFN-receptor knockout mice. These results indicate that Glu333 contributes to RABV attenuation by determining the ability of the virus to infect astrocytes and stimulate subsequent IFN responses.
• Refeeding activates neurons in the dorsomedial hypothalamus to inhibit food intake and promote positive valence
  Daigo Imoto; Izumi Yamamoto; Hirokazu Matsunaga; Toya Yonekura; Ming-Liang Lee; Kan X. Kato; Takeshi Yamasaki; Shucheng Xu; Taiga Ishimoto; Satoshi Yamagata; Ken-ichi Otsuguro; Motohiro Horiuchi; Norifumi Iijima; Kazuhiro Kimura; Chitoku Toda
  Molecular Metabolism, 54, 101366, 101366, Elsevier BV, Oct. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVE: The regulation of food intake is a major research area in the study of obesity, which plays a key role in the development of metabolic syndrome. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behavior, but the deletion of a gene has a long-term effect on neurophysiology. Our understanding of short-term changes such as appetite under physiological conditions is therefore still limited. METHODS: Targeted recombination in active populations (TRAP) is a newly developed method for labeling active neurons by using tamoxifen-inducible Cre recombination controlled by the promoter of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), a member of immediate early genes. Transgenic mice for TRAP were fasted overnight, re-fed with normal diet, and injected with 4-hydroxytamoxifen 1 h after the refeeding to label the active neurons. The role of labeled neurons was examined by expressing excitatory or inhibitory designer receptors exclusively activated by designer drugs (DREADDs). The labeled neurons were extracted and RNA sequencing was performed to identify genes that are specifically expressed in these neurons. RESULTS: Fasting-refeeding activated and labeled neurons in the compact part of the dorsomedial hypothalamus (DMH) that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of the labeled DMH neurons decreased food intake and developed place preference, an indicator of positive valence. Chemogenetic activation or inhibition of these neurons had no influence on the whole-body glucose metabolism. The labeled DMH neurons expressed prodynorphin (pdyn), gastrin-releasing peptide (GRP), cholecystokinin (CCK), and thyrotropin-releasing hormone receptor (Trhr) genes. CONCLUSIONS: We identified a novel cell type of DMH neurons that can inhibit food intake and promote feeding-induced positive valence. Our study provides insight into the role of DMH and its molecular mechanism in the regulation of appetite and emotion.
• Hydrogen sulfide induces Ca2+ release from intracellular Ca2+ stores and stimulates lactate production in spinal cord astrocytes.
  Takeshi Nii; Ryota Eguchi; Ken-Ichi Otsuguro
  Neuroscience research, 171, 67, 73, Oct. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Hydrogen sulfide (H2S) is a well-known inhibitor of the mitochondrial electron transport chain (ETC). H2S also increases intracellular Ca2+ levels in astrocytes, which are glial cells and that supply lactate as an energy substrate to neurons. Here, we examined the relationship between H2S-induced metabolic changes and Ca2+ responses in spinal cord astrocytes. Na2S (150 μM), an H2S donor, increased the intracellular Ca2+ concentration, which was inhibited by an ETC inhibitor and an uncoupler of mitochondrial oxidative phosphorylation. Na2S also increased the accumulation of extracellular lactate. Na2S alone did not change intracellular ATP content, but decreased it when glycolysis was inhibited. The Na2S-induced Ca2+ increase and accumulation of extracellular lactate were inhibited by emetine, an inhibitor of translocon complex, which mediates Ca2+ leak from the endoplasmic reticulum (ER). Furthermore, an inhibitor of the Ca2+-sensitive NADH shuttle decreased Na2S-mediated accumulation of lactate. We conclude that inhibition of the mitochondrial ETC by H2S induces Ca2+ release from mitochondria and the ER in spinal cord astrocytes, which increases lactate production. H2S may promote glycolysis by activating the Ca2+-sensitive NADH shuttle and facilitating the supply of lactate from astrocytes to neurons.
• Alpha and beta adrenoceptors activate interleukin-6 transcription through different pathways in cultured astrocytes from rat spinal cord
  Kohei Morimoto; Ryota Eguchi; Taisuke Kitano; Ken-ichi Otsuguro
  Cytokine, 142, 155497, 155497, Elsevier BV, Jun. 2021, [Peer-reviewed], [Last author, Corresponding author]
  Scientific journal
• Opposing functions of α- and β-adrenoceptors in the formation of processes by cultured astrocytes.
  Taisuke Kitano; Ryota Eguchi; Yuko Okamatsu-Ogura; Soichiro Yamaguchi; Ken-Ichi Otsuguro
  Journal of Pharmacological Sciences, 145, 3, 228, 240, Elsevier BV, Mar. 2021, [Peer-reviewed], [Last author, Corresponding author], [Domestic magazines]
  English, Scientific journal, Astrocytes are glial cells with numerous fine processes which are important for the functions of the central nervous system. The activation of β-adrenoceptors induces process formation of astrocytes via cyclic AMP (cAMP) signaling. However, the role of α-adrenoceptors in the astrocyte morphology has not been elucidated. Here, we examined it by using cultured astrocytes from neonatal rat spinal cords and cortices. Exposure of these cells to noradrenaline and the β-adrenoceptor agonist isoproterenol increased intracellular cAMP levels and induced the formation of processes. Noradrenaline-induced process formation was enhanced with the α1-adrenoceptor antagonist prazosin and α2-adrenoceptor antagonist atipamezole. Atipamezole also enhanced noradrenaline-induced cAMP elevation. Isoproterenol-induced process formation was not inhibited by the α1-adrenoceptor agonist phenylephrine but was inhibited by the α2-adrenoceptor agonist dexmedetomidine. Dexmedetomidine also inhibited process formation induced by the adenylate cyclase activator forskolin and the membrane-permeable cAMP analog dibutyryl-cAMP. Moreover, dexmedetomidine inhibited cAMP-independent process formation induced by adenosine or the Rho-associated kinase inhibitor Y27632. In the presence of propranolol, noradrenaline inhibited Y27632-induced process formation, which was abolished by prazosin or atipamezole. These results demonstrate that α-adrenoceptors inhibit both cAMP-dependent and -independent astrocytic process formation.
• [Responses to the COVID-19 pandemic and its impacts on pharmacology education in the universities and colleges in Japan: nationwide emergency survey jointly conducted by the Physiological Society of Japan and the Japanese Pharmacological Society].
  Masaki Mogi; Tomoyuki Furuyashiki; Kazuhiro Takuma; Ken-Ichi Otsuguro; Satoshi Tanaka; Masabumi Minami
  Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 156, 6, 324, 329, 2021, [Domestic magazines]
  Japanese, Scientific journal, With the spread of new coronavirus infections (COVID-19), universities/colleges have transformed their educational format from conventional group education to distance learning. In order to share information on the new educational format among the members of the society, the Physiological Society of Japan and the Japanese Pharmacological Society (JPS) jointly conducted the "Emergency Joint Survey on Responses of Universities to COVID-19 and Its Impact on Physiology and Pharmacology Education". The JPS surveyed pharmacology departments/divisions at schools of pharmacy, medicine, dentistry, and veterinary medicine in 202 universities (response rate 89%) from August to September 2020. 85% of the universities changed the lecture method, and 70% changed the practical training. 30%, 30%, and 40% of the lectures were live, on-demand, and mixed (combination of live and on-demand) lectures, respectively. 25% of the practical training was live or a combination of live and on-demand lectures, and 45% was on-demand delivery. There are many problems to do online methods such as stable network environment, lack of the reality for students and difficulty of the check of their understanding. On the other hand, there are unexpected benefits in online methods such as anytime learning, an increase in questions from students and repeatable learning. More than 60% considered employing the newly introduced educational styles even after the pandemic. Students' mental health problems and disruption of daily rhythms, quality assurance of online education, and copyright issues were also concerned. Pharmacology education faces a significant turning point in introducing and improving distance learning with or post the COVID-19 pandemic.
• Hydrogen sulfide induces Ca²⁺ release from the endoplasmic reticulum and suppresses ATP-induced Ca²⁺ signaling in rat spinal cord astrocytes
  Nii T; Eguchi R; Yamaguchi S; Otsuguro K
  EUROPEAN JOURNAL OF PHARMACOLOGY, 891, 173684, 173684, Elsevier BV, Jan. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Hydrogen sulfide (H2S) has a variety of physiological functions. H2S reportedly increases intracellular Ca2+ concentration ([Ca2+]i) in astrocytes. However, the precise mechanism and functional role of this increase are not known. Here, we examined the effects of H2S on [Ca2+]i in astrocytes from the rat spinal cord and whether H2S affects ATP-induced Ca2+ signaling, which is known to be involved in synaptic function. Na2S (150 μM), an H2S donor, produced a nontoxic increase in [Ca2+]i. The [Ca2+]i increase by Na2S was inhibited by Ca2+ depletion in the endoplasmic reticulum (ER) but not by removal of extracellular Ca2+, indicating that H2S releases Ca2+ from the ER. On the other hand, Na2S inhibited ATP-induced [Ca2+]i increase when Na2S clearly increased [Ca2+]i in the astrocytes, which was not suppressed by a reducing agent. In addition, Na2S had no effect on intracellular cyclic AMP (cAMP) level. These results indicate that oxidative post-translational modification of proteins and cAMP are not involved in the inhibitory effect of H2S on ATP-induced Ca2+ signaling. We conclude that H2S indirectly inhibits ATP-induced Ca2+ signaling by decreasing Ca2+ content in the ER in astrocytes. In this way, H2S may influence intercellular communication between astrocytes and neurons, thereby contributing to neuronal signaling in the nervous system.
• Fibroblast growth factor 2 upregulates ecto-5′-nucleotidase and adenosine deaminase via MAPK pathways in cultured rat spinal cord astrocytes
  Ryota Eguchi; Taisuke Kitano; Ken-ichi Otsuguro
  Purinergic Signalling, 16, 4, 519, 527, Springer Science and Business Media LLC, Dec. 2020, [Peer-reviewed], [Last author]
  English, Scientific journal
• A Mechanosensitive Channel, Mouse Transmembrane Channel-Like Protein 1 (mTmc1) is Translated from a Splice Variant mTmc1ex1 but Not from the Other Variant mTmc1ex2.
  Yamaguchi S; Hamamura M; Otsuguro K
  Int J Mol Sci, 21, 18, 04 Sep. 2020, [Peer-reviewed], [Last author], [International Magazine]
  English, Scientific journal, Mechanical stimuli caused by sound waves are detected by hair cells in the cochlea through the opening of mechanoelectrical transduction (MET) channels. Transmembrane channel-like protein 1 (TMC1) has been revealed to be the pore-forming component of the MET channel. The two splice variants for mouse Tmc1 (mTmc1ex1 and mTmc1ex2) were reported to be expressed in the cochlea of infant mice, though only the sequence of mTmc1ex2 had been deposited in GenBank. However, due to the presence of an upstream open reading frame (uORF) and the absence of a typical Kozak sequence in mTmc1ex2, we questioned whether mTMC1 was translated from mTmc1ex2. Therefore, in this study, we evaluated which splice variant was protein-coding mRNA. Firstly, the results of RT-PCR and cDNA cloning of mTmc1 using mRNA isolated from the cochlea of five-week-old mice suggested that more Tmc1ex1 were expressed than mTmc1ex2. Secondly, mTMC1 was translated from mTmc1ex1 but not from mTmc1ex2 in a heterologous expression system. Finally, analyses using site-directed mutagenesis revealed that the uORF and the weak Kozak sequence in mTmc1ex2 prevented the translation of mTMC1 from mTmc1ex2. These results suggest that mTmc1ex1 plays a main role in the expression of mTMC1 in the mouse cochlea, and therefore, mTmc1ex1 should be the mRNA for mTMC1 hereafter.
• Bidirectional modulation of TNF-α transcription via α- and β-adrenoceptors in cultured astrocytes from rat spinal cord.
  Morimoto K; Kitano T; Eguchi R; Otsuguro K
  Biochem Biophys Res Commun, 528, 78, 84, 22 May 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Noradrenaline (NA) suppresses TNF-α production via β-adrenoceptors (ARs) in brain astrocytes. However, the downstream pathways from β-ARs, and the involvement of α-ARs, remains unknown. In this study, we investigated the AR-mediated regulation of TNF-α mRNA levels in cultured astrocytes from rat spinal cord. NA, the α1-agonist phenylephrine, and the β-agonist isoproterenol decreased the TNF-α mRNA level, while the α2-agonist dexmedetomidine increased it. The isoproterenol-induced TNF-α mRNA decrease was accompanied by a decrease in ERK phosphorylation. An adenylyl cyclase activator and an ERK inhibitor mimicked these effects. These results indicate that the transcriptional regulation of TNF-α by β-ARs is mediated via cAMP pathways followed by the ERK pathway inhibition. The dexmedetomidine-induced TNF-α mRNA increase was accompanied by phosphorylation of JNK and ERK, which was blocked by a JNK inhibitor. Furthermore, the LPS-induced increase in the TNF-α mRNA level was accompanied by NF-κB nuclear translocation, and both these effects were blocked by phenylephrine. An NF-κB inhibitor suppressed the LPS-induced increase in the TNF-α mRNA level. These results suggest that α1-ARs suppress the LPS-induced increase in the TNF-α mRNA level via inhibition of NF-κB nuclear translocation. Taken together, our study reveals that both α- and β-ARs are involved in the transcriptional regulation of TNF-α in astrocytes.
• TRPM4 and TRPM5 Channels Share Crucial Amino Acid Residues for Ca²⁺ Sensitivity but Not Significance of PI(4,5)P₂.
  Yamaguchi S; Tanimoto A; Iwasa S; Otsuguro K
  Int J Mol Sci, 20, 8, E2012, Apr. 2019, [Peer-reviewed], [Last author], [International Magazine]
  English, Scientific journal, Transient receptor potential melastatin member 4 (TRPM4) and 5 (TRPM5) channels are Ca2+-activated nonselective cation channels. Intracellular Ca2+ is the most important regulator for them to open, though PI(4,5)P2, a membrane phosphoinositide, has been reported to regulate their Ca2+-sensitivities. We previously reported that negatively-charged amino acid residues near and in the TRP domain are necessary for the normal Ca2+ sensitivity of TRPM4. More recently, a cryo-electron microscopy structure of Ca2+-bound (but closed) TRPM4 was reported, proposing a Ca2+-binding site within an intracellular cavity formed by S2 and S3. Here, we examined the functional effects of mutations of the amino acid residues related to the proposed Ca2+-binding site on TRPM4 and also TRPM5 using mutagenesis and patch clamp techniques. The mutations of the amino acid residues of TRPM4 and TRPM5 reduced their Ca2+-sensitivities in a similar way. On the other hand, intracellular applications of PI(4,5)P2 recovered Ca2+-sensitivity of desensitized TRPM4, but its effect on TRPM5 was negligible. From these results, the Ca2+-binding sites of TRPM4 and TRPM5 were shown to be formed by the same amino acid residues by functional analyses, but the impact of PI(4,5)P2 on the regulation of TRPM5 seemed to be smaller than that on the regulation of TRPM4.
• The α_2A -adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine.
  Kitano T; Kobayashi T; Yamaguchi S; Otsuguro K
  J Vet Pharmacol Ther, 42, 2, 243, 247, Wiley, Mar. 2019, [Peer-reviewed], [Last author, Corresponding author]
  Scientific journal
• Fibroblast growth factor 2 modulates extracellular purine metabolism by upregulating ecto-5'-nucleotidase and adenosine deaminase in cultured rat spinal cord astrocytes.
  Eguchi R; Yamaguchi S; Otsuguro K
  Journal of pharmacological sciences, 139, 2, 98, 104, Feb. 2019, [Peer-reviewed], [Last author, Corresponding author]
• IL-1β augments H2S-induced increase in intracellular Ca2+ through polysulfides generated from H2S/NO interaction
  Ayako Ujike; Tomoki Kuraishi; Soichiro Yamaguchi; Ryota Eguchi; Taisuke Kitano; Jumpei Kamise; Shigeo Ito; Ken-ichi Otsuguro
  European Journal of Pharmacology, 821, 88, 96, Elsevier B.V., 15 Feb. 2018, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Intracellular diminazene aceturate content and adenosine incorporation in diminazene aceturate-resistant Babesia gibsoni isolate in vitro
  Masahiro Yamasaki; Nao Watanabe; Natsuki Idaka; Tohru Yamamori; Ken-ichi Otsuguro; Naohiro Uchida; Aiko Iguchi; Hiroshi Ohta; Mitsuyoshi Takiguchi
  EXPERIMENTAL PARASITOLOGY, 183, 92, 98, Dec. 2017, [Peer-reviewed]
  English, Scientific journal
• A mechanically activated ion channel is functionally expressed in the MrgprB4 positive sensory neurons, which detect stroking of hairy skin in mice
  Soichiro Yamaguchi; Ken-ichi Otsuguro
  NEUROSCIENCE LETTERS, 653, 139, 145, Jul. 2017, [Peer-reviewed], [Last author]
  English, Scientific journal
• Hydrogen sulfide activates TRPA1 and releases 5-HT from epithelioid cells of the chicken thoracic aorta
  Dugar Delgermurun; Soichiro Yamaguchi; Osamu Ichii; Yasuhiro Kon; Shigeo Ito; Ken-ichi Otsuguro
  COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, 187, 43, 49, Sep. 2016, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Endogenous 5-HT outflow from chicken aorta by 5-HT uptake inhibitors and amphetamine derivatives
  Dugar Delgermurun; Shigeo Ito; Toshio Ohta; Soichiro Yamaguchi; Ken-ichi Otsuguro
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 1, 71, 76, Jan. 2016, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat
  Ken-ichi Otsuguro; Yuki Tomonari; Saori Otsuka; Soichiro Yamaguchi; Yasuhiro Kon; Shigeo Ito
  NEUROPHARMACOLOGY, 97, 160, 170, Oct. 2015, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Bidirectional effects of hydrogen sulfide via ATP-sensitive K+ channels and transient receptor potential A1 channels in RIN14B cells
  Ayako Ujike; Ken-ichi Otsuguro; Ryo Miyamoto; Soichiro Yamaguchi; Shigeo Ito
  EUROPEAN JOURNAL OF PHARMACOLOGY, 764, 463, 470, Oct. 2015, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Contribution of alpha(2A)-adrenoceptor subtype to effect of dexmedetomidine and xylazine on spinal synaptic transmission of mice
  Takeshi Kobayashi; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito
  EUROPEAN JOURNAL OF PHARMACOLOGY, 761, 321, 329, Aug. 2015, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Neuronal regulation of expression of hydrogen sulfide-producing enzyme cystathionine beta-synthase in rat spinal cord astrocytes
  Ryo Miyamoto; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito
  NEUROSCIENCE RESEARCH, 97, 52, 59, Aug. 2015, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Different mechanisms of extracellular adenosine accumulation by reduction of the external Ca2+ concentration and inhibition of adenosine metabolism in spinal astrocytes
  Ryota Eguchi; Sanae Akao; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 128, 1, 47, 53, May 2015, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Negatively Charged Amino Acids Near and in Transient Receptor Potential (TRP) Domain of TRPM4 Channel Are One Determinant of Its Ca2+ Sensitivity
  Soichiro Yamaguchi; Akira Tanimoto; Ken-ichi Otsuguro; Hiroshi Hibino; Shigeo Ito
  JOURNAL OF BIOLOGICAL CHEMISTRY, 289, 51, 35265, 35282, Dec. 2014, [Peer-reviewed]
  English, Scientific journal
• Contribution of cysteine aminotransferase and mercaptopyruvate sulfurtransferase to hydrogen sulfide production in peripheral neurons
  Ryo Miyamoto; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito
  JOURNAL OF NEUROCHEMISTRY, 130, 1, 29, 40, Jul. 2014, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Endogenously released 5-HT inhibits A and C fiber-evoked synaptic transmission in the rat spinal cord by the facilitation of GABA/glycine and 5-HT release via 5-HT2A and 5-HT3 receptors
  Takeyuki Iwasaki; Ken-ichi Otsuguro; Takeshi Kobayashi; Toshio Ohta; Shigeo Ito
  EUROPEAN JOURNAL OF PHARMACOLOGY, 702, 1-3, 149, 157, Feb. 2013, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1-like receptors in neonatal rats
  K. Kawamoto; K. Otsuguro; M. Ishizuka; S. Ito
  BRITISH JOURNAL OF PHARMACOLOGY, 166, 2, 788, 800, May 2012, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Differential contributions of adenosine to hypoxia-evoked depressions of three neuronal pathways in isolated spinal cord of neonatal rats
  K. Otsuguro; M. Wada; S. Ito
  BRITISH JOURNAL OF PHARMACOLOGY, 164, 1, 132, 144, Sep. 2011, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Time- and concentration-dependent activation of TRPA1 by hydrogen sulfide in rat DRG neurons
  Ryo Miyamoto; Ken-ichi Otsuguro; Shigeo Ito
  NEUROSCIENCE LETTERS, 499, 2, 137, 142, Jul. 2011, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Adenosine and inosine release during hypoxia in the isolated spinal cord of neonatal rats
  T. Takahashi; K. Otsuguro; T. Ohta; S. Ito
  BRITISH JOURNAL OF PHARMACOLOGY, 161, 8, 1806, 1816, Dec. 2010, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• HISTAMINE POTENTIATES ACID-INDUCED RESPONSES MEDIATING TRANSIENT RECEPTOR POTENTIAL V1 IN MOUSE PRIMARY SENSORY NEURONS
  Y. Kajihara; M. Murakami; T. Imagawa; K. Otsuguro; S. Ito; T. Ohta
  NEUROSCIENCE, 166, 1, 292, 304, Mar. 2010, [Peer-reviewed]
  English, Scientific journal
• Effects of prasugrel, a novel P2Y(12) inhibitor, in rat models of cerebral and peripheral artery occlusive diseases
  Taketoshi Ogawa; Masami Hashimoto; Yoichi Niitsu; Joseph A. Jakubowski; Yoshiro Tani; Ken-ichi Otsuguro; Fumitoshi Asai; Atsuhiro Sugidachi
  EUROPEAN JOURNAL OF PHARMACOLOGY, 612, 1-3, 29, 34, Jun. 2009, [Peer-reviewed]
  English, Scientific journal
• Roles of purines in synaptic modulation evoked by hypercapnia in isolated spinal cord of neonatal rat in vitro
  K. Otsuguro; M. Ban; T. Ohta; S. Ito
  BRITISH JOURNAL OF PHARMACOLOGY, 156, 7, 1167, 1177, Apr. 2009, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Voltage-gated channel properties of epithelial cells in porcine vomeronasal organ
  Tetsuya Ishida; Ryo Takei; Shree Hari Gautam; Ken-ichi Otsuguro; Toshio Ohta; Shigeo Ito; Yoshiaki Habara; Toshiyuki Saito
  NEUROSCIENCE LETTERS, 441, 3, 277, 281, Aug. 2008, [Peer-reviewed]
  English, Scientific journal
• Isoform-specific Inhibition of TRPC4 Channel by Phosphatidylinositol 4,5-Bisphosphate
  Ken-ichi Otsuguro; Jisen Tang; Yufang Tang; Rui Xiao; Marc Freichel; Volodymyr Tsvilovskyy; Shigeo Ito; Veit Flockerzi; Michael X. Zhu; Alexander V. Zholos
  JOURNAL OF BIOLOGICAL CHEMISTRY, 283, 15, 10026, 10036, Apr. 2008, [Peer-reviewed], [Lead author]
  English, Scientific journal
• Repeat oral dosing of prasugrel, a novel P2Y(12) receptor inhibitor, results in cumulative and potent antiplatelet and antithrombotic activity in several animal species
  Yoichi Niitsu; Atsuhiro Sugidachi; Taketoshi Ogawa; Joseph A. Jakubowski; Masami Hashimoto; Takashi Isobe; Ken-ichi Otsuguro; Fumitoshi Asai
  EUROPEAN JOURNAL OF PHARMACOLOGY, 579, 1-3, 276, 282, Jan. 2008, [Peer-reviewed]
  English, Scientific journal
• Involvement of prostaglandin E-2 derived from enteric glial cells in the action of bradykinin in cultured rat myenteric neurons
  M. Murakami; T. Ohta; K. -I. Otsuguro; S. Ito
  NEUROSCIENCE, 145, 2, 642, 653, Mar. 2007, [Peer-reviewed]
  English, Scientific journal
• T-type Ca2+ channels mediate propagation of odor-induced Ca2+ transients in rat olfactory receptor neurons
  S. H. Gautam; K. -I. Otsuguro; S. Ito; T. Saito; Y. Habara
  NEUROSCIENCE, 144, 2, 702, 713, Jan. 2007, [Peer-reviewed]
  English, Scientific journal
• T-type Ca2+ channels contribute to IBMX/forskolin- and K+-induced Ca2+ transients in porcine olfactory receptor neurons
  Shree Hari Gautam; Ken-ichi Otsuguro; Shigeo Ito; Toshiyuki Saito; Yoshiaki Habara
  NEUROSCIENCE RESEARCH, 57, 1, 129, 139, Jan. 2007, [Peer-reviewed]
  English, Scientific journal
• Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons
  Toshio Ohta; Yuki Ikemi; Matsuka Murakami; Toshiaki Imagawa; Ken-ichi Otsuguro; Shigeo Ito
  JOURNAL OF PHYSIOLOGY-LONDON, 576, 3, 809, 822, Nov. 2006, [Peer-reviewed]
  English, Scientific journal
• Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats
  Ken-ichi Otsuguro; Yoshihiko Yamaji; Masaaki Ban; Toshio Ohta; Shigeo Ito
  JOURNAL OF PHYSIOLOGY-LONDON, 574, 3, 835, 847, Aug. 2006, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Intensity of odorant stimulation affects mode of Ca2+ dynamics in rat olfactory receptor neurons
  Shree Hari Gautam; Ken-ichi Otsuguro; Shigeo Ito; Toshiyuki Saito; Yoshiaki Habara
  NEUROSCIENCE RESEARCH, 55, 4, 410, 420, Aug. 2006, [Peer-reviewed]
  English, Scientific journal
• Zinc modulates primary afferent fiber-evoked responses of ventral roots in neonatal rat spinal cord in vitro
  K Otsuguro; T Ohta; S Ito
  NEUROSCIENCE, 138, 1, 281, 291, 2006, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Molecular cloning, functional characterization of the porcine transient receptor potential V1 (pTRPV1) and pharmacological comparison with endogenous pTRPV1
  T Ohta; R Komatsu; T Imagawa; K Otsuguro; S Ito
  BIOCHEMICAL PHARMACOLOGY, 71, 1-2, 173, 187, Dec. 2005, [Peer-reviewed]
  English, Scientific journal
• P2X(2) receptors are essential for [Ca2+](i) increases in response to ATP in cultured rat myenteric neurons
  T Ohta; A Kubota; M Murakami; K Otsuguro; S Ito
  AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 289, 5, G935, G948, Nov. 2005, [Peer-reviewed]
  English, Scientific journal
• Effects of opioid receptor and alpha(2)-adrenoceptor agonists on slow ventral root potentials and on capsaicin and fonnalin tests in neonatal rats
  K Otsuguro; S Yasutake; T Ohta; S Ito
  DEVELOPMENTAL BRAIN RESEARCH, 158, 1-2, 50, 58, Aug. 2005, [Peer-reviewed], [Lead author]
  English, Scientific journal
• Characterization of forskolin-induced Ca2+ signals in rat olfactory receptor neurons
  K Otsuguro; SH Gautam; S Ito; Y Habara; T Saito
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 97, 4, 510, 518, Apr. 2005, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery
  Y Suzuki; K Kondo; Y Matsumoto; BQ Zhao; K Otsuguro; T Maeda; Y Tsukamoto; T Urano; K Umemura
  LIFE SCIENCES, 73, 10, 1289, 1298, Jul. 2003, [Peer-reviewed]
  English, Scientific journal
• Platelet alpha-granule secretion and its modification by SC-57101A, a GPIIb/IIIa antagonist
  T Ogawa; A Sugidachi; K Otsuguro; T Isobe; F Asai
  BIOCHEMICAL PHARMACOLOGY, 63, 10, 1911, 1918, May 2002, [Peer-reviewed]
  English, Scientific journal
• Antiplatelet action of R-99224, an active metabolite of a novel thienopyridine-type G(i)-linked P2T antagonist, CS-747
  A Sugidachi; F Asai; K Yoneda; R Iwamura; T Ogawa; K Otsuguro; H Koike
  BRITISH JOURNAL OF PHARMACOLOGY, 132, 1, 47, 54, Jan. 2001, [Peer-reviewed]
  English, Scientific journal
• Two types of relaxation-mediating P-2 receptors in rat gastric circular muscle
  K Otsuguro; T Ohta; S Ito; Y Nakazato
  JAPANESE JOURNAL OF PHARMACOLOGY, 78, 2, 209, 215, Oct. 1998, [Peer-reviewed], [Lead author]
  English, Scientific journal
• Influence of purines and pyrimidines on circular muscle of the rat proximal stomach
  K Otsuguro; S Ito; T Ohta; Y Nakazato
  EUROPEAN JOURNAL OF PHARMACOLOGY, 317, 1, 97, 105, Dec. 1996, [Peer-reviewed], [Lead author]
  English, Scientific journal
• Modulation of calcium current by ATP in guinea-pig adrenal chromaffin cells
  K Otsuguro; T Ohta; S Ito; Y Nakazato
  PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 431, 3, 402, 407, Jan. 1996, [Peer-reviewed], [Lead author]
  English, Scientific journal
• Muscarinic receptor subtypes mediating catecholamine secretion and increase in intracellular Ca2+ concentration in adrenal chromaffin cells of the guinea pig
  T Asano; T Ohta; K Otsuguro; S Ito; Y Nakazato
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 57, 6, 1067, 1071, Dec. 1995, [Peer-reviewed]
  English, Scientific journal
• Characteristics of ATP-induced catecholamine secretion from adrenal chromaffin cells of the guinea-pig
  Asano, T; Otsuguro, K; Ohta, T; Sugawara, T; Ito, S; Nakazato, Y
  Comparative Biochemistry and Physiology C-Pharmacology Toxicology & Endocrinology, 112, 2, 101, 108, Oct. 1995, [Peer-reviewed]
  Scientific journal
• ATP-EVOKED MEMBRANE CURRENT IN GUINEA-PIG ADRENAL CHROMAFFIN CELLS
  K OTSUGURO; T ASANO; T OHTA; S ITO; Y NAKAZATO
  NEUROSCIENCE LETTERS, 187, 3, 145, 148, Mar. 1995, [Peer-reviewed], [Lead author]
  English, Scientific journal

• レバミピドはコレシストキニン1受容体を介してドライアイの痛覚過敏を抑制する
  田川義晃; 野田航介; 乙黒兼一; 村田美幸; 石田晋, 日本眼薬理学会プログラム・講演抄録集, 42nd, 2022
• Hydrogen sulfide modulates cellular functions via ion channels
  Otsuguro K, Sulphuric acid and industry, 70, 12, 163, 169, Dec. 2017, [Invited], [Lead author]
  Japanese, Introduction commerce magazine
• 三叉神経節細胞におけるレバミピドのコレシストキニン経路抑制機序の検討
  田川 義晃; 野田 航介; 宮本 亮; 乙黒 兼一; 石塚 タンエルダル; 神田 敦宏; 石田 晋, 日本眼科学会雑誌, 121, 臨増, 221, 221, Mar. 2017
  (公財)日本眼科学会, Japanese
• Suppression of Cholecystokinin Response by Rebamipide in Trigeminal Ganglion Cells
  Yoshiaki Tagawa; Kousuke Noda; Ryo Miyamoto; Ken-ichi Otsuguro; Erdal Tan Ishizuka; Takeshi Ohguchi; Atsuhiro Kanda; Susumu Ishida, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, 12, Sep. 2016
  English, Summary international conference
• 鶏胸大動脈におけるグロムス細胞からの5-HT放出に対するH2Sの作用(Effect of H2S on 5-HT release from glomus cells in the chicken thoracic aorta)
  Delgermurun Dugar; 山口 聡一郎; 市居 修; 昆 泰寛; 伊藤 茂男; 乙黒 兼一, 日本獣医学会学術集会講演要旨集, 159回, 495, 495, Aug. 2016
  (公社)日本獣医学会, English
• レバミピドは三叉神経節細胞におけるコレシストキニン応答を抑制する
  田川 義晃; 野田 航介; 宮本 亮; 乙黒 兼一; 石塚 タンエルダル; 神田 敦宏; 石田 晋, 日本眼科学会雑誌, 120, 臨増, 232, 232, Mar. 2016
  (公財)日本眼科学会, Japanese
• Rebamipide Reduces the Response to Capsaicin in Sensory Ganglion Cells
  Yoshiaki Tagawa; Kousuke Noda; Ryo Miyamoto; Ken-ichi Otsuguro; Erdal Tan Ishizuka; Saori Inafuku; Takeshi Ohguchi; Atsuhiro Kanda; Susumu Ishida, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56, 7, Jun. 2015
  English, Summary international conference
• CYSTEINE AMINOTRANSFERASE AND MERCAPTOPYRUVATE SULFURTRANSFERASE CONTRIBUTE TO HYDROGEN SULFIDE PRODUCTION IN THE PERIPHERAL NERVOUS SYSTEM
  R. Miyamoto; K. Otsuguro; S. Yamaguchi; S. Ito, BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 115, 258, 259, Jul. 2014
  English, Summary international conference
• HYDROGEN SULFIDE BIDIRECTIONALLY MODULATES CA2+SIGNALS IN RIN14B CELLS
  A. Ujike; K. Otsuguro; R. Miyamoto; S. Yamaguchi; S. Ito, BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 115, 264, 264, Jul. 2014
  English, Summary international conference
• H2S production in peripheral neurons is mediated by cysteine aminotransferase and mercaptopyruvate sulfurtransferase
  Ryo Miyamoto; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito, NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 39, S34, S34, May 2014
  English, Summary international conference
• The bidirectional effect of hydrogen sulfide on Ca2+ signals via opening K-ATP and TRPA1 channels in RIN14B cells
  Ayako Ujike; Ken-ichi Otsuguro; Ryo Miyamoto; Soichiro Yamaguchi; Shigeo Ito, NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 39, S37, S38, May 2014
  English, Summary international conference
• Inhibitory and excitatory effects of hydrogen sulfide on RIN14B cells
  Ayako Ujike; Ken-ichi Otsuguro; Ryo Miyamoto; Soichiro Yamaguchi; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 165P, 165P, 2014
  English, Summary international conference
• Contribution of CAT/MPST to H2S production in peripheral neurons
  Ryo Miyamoto; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 191P, 191P, 2014
  English, Summary international conference
• Increase in extracellular adenosine level by adenosine metabolic enzyme inhibitors and removal of extracellular Ca2+ in rat spinal astrocytes
  Sanae Masumoto; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 215P, 215P, 2013
  English, Summary international conference
• Contribution of alpha(2A) adrenoceptor to effect of alpha(2) agonists on spinal reflex potential
  Takeshi Kobayashi; Ken-ichi Otsuguro; Soichiro Yamaguchi; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 213P, 213P, 2013
  English, Summary international conference
• Increase in intracellular Ca2+ concentration induced by hydrogen sulfide in RIN14B cells
  Ayako Ujike; Ken-ichi Otsuguro; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 118, 210P, 210P, 2012
  English, Summary international conference
• 高磁場BOLD-fMRIで観察された侵害刺激に対するラット大脳皮質帯状回における情動応答のc-Fos発現の免疫組織化学的評価による検討
  古賀智之; 佐藤裕之; 安井博宣; 乙黒兼一; 日高勇一; 木曽哲男; 高橋正泰; 井上達雄; 藤川昭彦; 稲波修; 伊藤茂男; 浅沼武敏, 日本獣医学会学術集会講演要旨集, 152nd, 2011
• Activation of Transient Receptor Potential Ankyrin 1 (TRPA1) in rat dorsal root ganglion neurons by hydrogen sulfide (H2S)
  Ryo Miyamoto; Ken-ichi Otsuguro; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 149P, 149P, 2011
  English, Summary international conference
• Effects of endogenous monoamines in the spinal cord of neonatal rats
  Kensuke Kawamoto; Takeyuki Iwasaki; Ken-ichi Otsuguro; Toshio Ohta; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 112, 131P, 131P, 2010
  English, Summary international conference
• Potentiation of TRPV1-mediated responses to protons by histamine in mouse primary sensory neurons
  Yuusuke Kajihara; Toshio Ohta; Ken-ichi Otsuguro; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 109, 78P, 78P, 2009
  English, Summary international conference
• The action of bradykinin in rat cultured myenteric neurons is modulated by prostaglandin E-2 released from enteric glial cells
  Matsuka Murakami; Ken-ichi Otsuguro; Toshio Ohta; Shigeo Ito, ACTA PHARMACOLOGICA SINICA, 27, 114, 114, Jul. 2006
  English, Summary international conference
• Involvement of adenosine in depression of spinal reflex activity during hypercapnic acidosis in isolated spinal cord of neonatal rat
  K Otsuguro; Y Yamaji; M Ban; T Ohta; S Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 123P, 123P, 2006
  English, Summary international conference
• 5-hydroxytryptamine potentiates transient receptor potential V1 functions in rat primary sensory neurons
  Toshio Ohta; Yuki Ikemi; Matsuka Murakami; Ken-ichi Otsuguro; Shigeo Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 101, 134, 134, 2006
  English, Summary international conference
• Involvement of enteric glial COX-PGE(2) pathway in responses of cultured rat myenteric neurons to bradykinin
  M Murakami; T Ohta; K Otsuguro; S Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 99P, 99P, 2006
  English, Summary international conference
• Potentiation of vanilloid receptor-mediated responses by 5-hydroxytryptamine in rat primary sensory neurons
  Y Ikemi; T Ohta; K Otsuguro; S Ito, JOURNAL OF PHARMACOLOGICAL SCIENCES, 97, 95P, 95P, 2005
  English, Summary international conference
• Effects of P-2-purinoceptor antagonists on purinoceptor- and pyrimidinoceptor-mediating contraction and relaxation in the rat gastric circular muscle
  K Otsuguro; T Ohta; S Ito; Y Nakazato, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 358, 1, R131, R131, 1998
  English, Summary international conference

• 薬理学・毒性学実験 第4版
  日本比較薬理学・毒性学会
  文栄堂出版, Mar. 2023, 9784830032868, [Contributor]
• 獣医薬理学（第二版）
  日本比較薬理学; 毒性学会
  近代出版, Mar. 2021, [Joint editor]
• 獣医臨床薬理学
  日本比較薬理学; 毒性学会
  近代出版, Dec. 2017, [Joint editor]
• 薬理学・毒性学実験 第3版
  日本比較薬理学; 毒性学会
  文栄堂出版, Apr. 2008, [Contributor]

• Investigation of analgesic effect of carbon dioxide in isolated spinal cord preparation - Alternative to in vivo pain tests- Section "Alternatives to animal use"
  Ken-ichi OTSUGURO
  The 2nd Joint Meeting of Veterinary Science in East Asia, 26 Apr. 2019, English, Nominated symposium
  [Invited], [International presentation]
• 北海道大学の動物実験教育の取り組み
  乙黒 兼一
  第161回日本獣医学会学術集会 第14回獣医学教育改革シンポジウム, 11 Sep. 2018, Japanese, Nominated symposium
  [Invited], [Domestic Conference]
• Effects of adenosine on spinal neuronal activities: its contribution to hypercapnia-evoked depression
  Ken-ichi OTSUGURO
  The 14th Seoul National University – Hokkaido University Joint Symposium, 18 Nov. 2011, English, Nominated symposium
  [Invited], [International presentation]
• 脊髄反射電位に対するアデノシンの作用と低酸素惹起シナプス伝達抑制への関与 シンポジウム「虚血病態の病態と治療」
  乙黒 兼一
  第38回 薬物活性シンポジウム, 11 Nov. 2010, Japanese, Nominated symposium
  [Invited], [Domestic Conference]
• 二酸化炭素の薬理作用
  乙黒 兼一
  第146回 日本獣医学会学術集会 日本実験動物医学会教育シンポジウム, 24 Sep. 2008, Japanese, Nominated symposium
  [Invited], [Domestic Conference]

• 獣医科学特別研究, 2024年, 博士後期課程, 獣医学院
• ケミカルハザード対策専門特論, 2024年, 博士後期課程, 獣医学院
• 獣医科学特論演習, 2024年, 博士後期課程, 獣医学院
• 生命科学特論, 2024年, 博士後期課程, 獣医学院
• 先端生命科学特論Ⅳ：薬理学, 2024年, 博士後期課程, 獣医学院
• 機能制御薬理学, 2024年, 学士課程, 獣医学部
• 基礎薬理学, 2024年, 学士課程, 獣医学部
• 臨床薬理学, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• 薬理学実習, 2024年, 学士課程, 獣医学部

• THE JAPANESE SOCIETY FOR NEUROCHEMISTRY
• 日本獣医学会
• 日本薬理学会

• アストロサイトによるグリンパティックシステムの制御機構
  科学研究費助成事業
  01 Apr. 2024 - 31 Mar. 2028
  乙黒 兼一
  日本学術振興会, 基盤研究(B), 北海道大学, 24K01916
• うつ病態におけるプリン動態変化とアストロサイト-ニューロン機能連関の役割の解明
  科学研究費助成事業
  Apr. 2021 - Mar. 2024
  乙黒 兼一
  本年度は、炎症性ストレスモデルとしてマウスにLPS（リポポリサッカライド）を投与した。マウスの活動量や飲水量に影響を与えない条件下で、強制水泳試験における不動時間の増加や、新規物体探索試験における探索時間の減少が示されたことから、うつ様行動の発現と短期記憶の障害が示唆された。エバンスブルー投与により血液脳関門の透過性を評価したが、透過性の増加は認められず、本実験条件では血液脳関門の破綻などは起きていないと考えられた。
  LPS投与後、アストロサイトとミクログリアの活性化の指標となるGFPA及びIba-1の発現増加が海馬において認められた。アストロサイトは突起数の増加などSholl分析で形態が複雑化していることが示されたが、反応性アストロサイトの指標となるマーカー分子に変化は見られなかった。また、ニューロンマーカーNeuNでの染色では海馬ニューロンの密度に変化はなかった。ゴルジ染色により海馬ニューロンのスパインを評価したところ、スパインの密度に変化は見られなかったが、未熟/成熟スパインの割合が増加していたことから、海馬でのシナプス伝達が変化していることが示唆された。
  脳の機能的変化とプリン動態との関連性を検討するために、脳内におけるプリン代謝関連分子のmRNA発現を調べた。複数のプリン代謝酵素の発現がLPS投与モデルにおいて増加、あるいは減少していることが確認され、脳内プリン動態の変化が脳機能に影響を与えている可能性がある。
  日本学術振興会, 基盤研究(C), 北海道大学, 21K05950
• ベクター媒介性感染症におけるベクター唾液の役割の解明
  基盤研究Ｂ
  2015 - 2018
  加藤 大智; 乙黒 兼一; 佐藤 晃一
  文部科学省 科学研究費助成事業, Competitive research funding
• 細胞外アデノシンデアミナーゼの分泌機構の解明
  奨励金・研究助成
  2018
  乙黒 兼一
  内藤記念科学振興財団, Principal investigator, Competitive research funding
• グリア伝達物質による脊髄アストロサイト機能の調節機構と病態下における役割の解明
  科研費種目ステップアップ支援事業
  2017
  乙黒 兼一
  北海道大学, Principal investigator, Competitive research funding
• シスタチオニンβ合成酵素の発現調節を介した新規中枢疾患治療ターゲットの探索
  研究奨励（一般）
  2017
  乙黒 兼一
  秋山記念生命科学振興財団, Principal investigator, Competitive research funding
• Gliotransmitter release and its protective effects in spinal astrocytes
  Grants-in-Aid for Scientific Research
  2014 - 2016
  Otsuguro Ken-ichi; YAMAGUCHI Soichiro
  Production and release mechanisms of adenosine and hydrogen sulfide (H2S), which are known to be neuroprotective agents, were examined in the cultured spinal astrocytes. Under the low Ca2+ conditions, ATP released by astrocytes was extracellularly degraded to adenosine, resulting in the increase in extracellular adenosine level. The astrocytic CBS (H2S synthase) expression was suggested to be controlled/maintained by the neurons. Adenosine and H2S affect cellular functions via the activation of receptors and ion channels. Under the ischemic conditions, it is suggested that the change in adenosine and H2S production and releases by the low Ca2+ and/or neuronal death is involved in disease onset and progression.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 26450440
• 中枢神経組織における硫化水素産生機構とアストロサイトの役割の解明
  研究助成金
  2015
  乙黒 兼一
  寿原記念財団, Principal investigator, Competitive research funding
• Quantitative analysis of nociceptive and motor reflexes in genetically modified mice
  Grants-in-Aid for Scientific Research
  Apr. 2011 - Mar. 2014
  ITO Shigeo; OTSUGURO Ken-ichi
  alpha-Adrenoceptor agonists, dexmedetomidine and xylazine inhibited spinal motor and nociceptive reflex potentials. In the alpha2A receptor-functional deficient D79N mice, the inhibitory effect on nociceptive but not motor reflex potentials by these agonists was attenuated. alpha2A-Receptors are suggested to be involved in the alpha2-agonist-evoked analgesia but not the inhibition of motor reflex. Adenosine and hydrogen sulfide (H2S) influence spinal neuronal activity. In the spinal astrocytes, the adenosine metabolic inhibitors released adenosine, while Ca2+-removal released ATP, which was degraded to adenosine. In the neurons, H2S is produced by the synthase CST/MPST.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23380170
• Species differences in nociceptive transmissions
  Grants-in-Aid for Scientific Research
  2011 - 2012
  ITO Shigeo; OTSUGURO Kenichi
  The effects of algesic and analgesic agents on the sensory neurons and spinal nociceptive pathways were examined to reveal the species differences in pain transmission. In the rat sensory neurons, the algesic agents, capsaicin and mustard oil, activated TRP channels. The electrophysiological features of spinal nociceptive reflex potentials and the effects of morphine in mice were similar to those in rats. Some differences in the effects of biogenic amines between rats and mice were observed, suggesting that there are species differences in pain control mechanisms by descending inhibitory neuronal pathways in the spinal cord.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 23658231
• Regulatory mechanisms of hydrogen sulfide in gastrointestinal functions: Is H2S an endogenous transmitter
  Grants-in-Aid for Scientific Research
  2011 - 2012
  OTSUGURO Kenichi; ITO Shigeo
  The effects of an hydrogen sulfide (H2S) donor, NaHS, on the sensory neurons and model cells (RIN14B) for enterochromaffin cells were examined. H2S increased intracellular Ca2+ levels via the activation of TRPA1, resulting in neuronal excitation and secretory responses. The neuronal model PC12 cells expressed AST (aspartate aminotransferase)/MPST (mercaptopyruvate sulfurtransferase) and generated H2S. In the intestine, it is suggested that neuronal cells not only respond to intraluminal H2S but also synthetizes H2S to regulate gastrointestinal functions.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 23658230
• Release of purines and its mechanisms under ischemic conditions in spinal cord
  Grants-in-Aid for Scientific Research(基盤研究(C))
  2008 - 2010
  Ken-ichi OTSUGURO
  It is well-known that hypoxia and acidosis significantly influence neuronal functions under ischemic conditions. In this study, an electrical activity of spinal neuronal pathways and extracellular purine concentration were measured. Hypoxia and acidosis released not only adenosine but also inosine from the spinal cord, and adenosine suppressed the neuronal activities via adenosine A1 receptors. In addition, the influence of hypoxia largely depended on age, temperature and neuronal pathways. It is suggested that adenosine plays an important role in this phenomenon.
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 20580317
• Quantitative analysis of pain response in isolated spinal cord and cultured dorsal root ganglion cell
  Grants-in-Aid for Scientific Research(基盤研究(B))
  2007 - 2009
  Shigeo ITO; Ken-ichi OTSUGURO
  We found that vanilloid receptor (TRPV1) channels, being key proteins for pain generation, were activated by mustard oil or methylsalicylate in addition to a vanilloid compound such as capsaicin and that the opening of the channels was controlled by extracellular Na^+ ions. It was demonstrated that histamine and 5-hydroxy- tryptamine, which were released at inflammation sites, augmented pain due to TRPV1 channel activation through respective receptors for these amines, and that adenosine release was associated with the analgesic action in response to hypercapnia.
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 19380163
• インスリンと顆粒球コロニー刺激因子(GCSF)の長期徐放製剤の開発に関する研究
  科学研究費補助金(萌芽研究)
  2007 - 2008
  伊藤 茂男; 梅村 孝司; 乙黒 兼一; 生駒 俊之
  1) 徐放担体の開発 : 以下の3点を調べた。(1) ヒドロキシアパタイト(HAP直径5μm)含有金属 : ポリ乳酸処理インスリン含有亜鉛(Zn)-HAP投与による血中インスリン濃度の増加は投与後2日で投与前のレベルに回復したが、投与したHAP中にインスリンは残留していた。鉄(Fe)-HAPとマグネシウム(Mg)-HAPを用いて、インスリンの徐放性を調べたが、Zn-HAPと同様、一過性の血糖低下作用と血中インスリン濃度増加作用しか示さなかった。(2)HAP粒子の大きさ : 直径2.5μmの脚と25μmのHAPをラットに皮下投与し、その消失速度を調べた。HAPの粒子径が小さくなると皮下投与部位からの消失速度が速まった(2.5μm ; 10日、5μm ; 14日、25μm ; 20日)。糖尿病ウサギにこれらインスリン含有HAPを投与して、血糖値と血中インスリン濃度変化を調べた結果、血糖低下反応とインスリン増加反応は投与後2日目で回復した。2.5μmの方が、インスリン増加は僅かに持続した。(3)薬物の併用 : インスリン-HAPをアルギン酸、カルボキシメチルセルロース(CMC)、デキサメサゾン(Dex)とともに投与したが、インスリン増加と血糖低下作用は一過性であった。2)製剤の毒性評価 : HAPのみ、CMC+HAP、アルギン酸+HAP、Dex+HAP、Fe-HAP、Mg-HAPを...
  文部科学省, 萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 19658107
• アシドーシスによる脊髄の機能変化
  研究奨励金
  2008
  乙黒 兼一
  上原記念生命科学財団, Principal investigator, Competitive research funding
• 病態動物モデルを用いた血管変性機序の解明
  大学教育の国際化推進プログラム（海外先進研究実践支援）
  Apr. 2006 - Mar. 2007
  乙黒 兼一
  文部科学省, Principal investigator, Competitive research funding
• 痛覚過敏における亜鉛トランスポーターの役割の解明
  科学研究費補助金(若手研究(B))
  2005 - 2006
  乙黒 兼一
  本研究の目的である摘出脊髄標本を用い、亜鉛の脊髄神経に与える影響を明らかにするため、新生ラットから摘出した脊髄半裁標本を用いて脊髄反射電位に対する亜鉛の効果を検討し、以下の結果を得た。1.脊髄後根を電気刺激すると、対応する前根からMSR(monosynaptic reflex potential)、fPSR(fast polysynaptic reflex potential)及びsVRP(slow ventral root potential)が、また隣接する後根からDRP(dorsal root potential)記録された。2.亜鉛は、MSR、fPSRには影響を与えず、sVRPに対しては低濃度(0.5-2μM)では抑制、高濃度(5及び10μM)では増強作用を示した。また高濃度亜鉛によってベース前根電位のわずかな脱分極が観察され、激しい自発活性の増加が生じる標本もあった。3.グリシン受容体拮抗薬ストリキニーネとGABA_A受容体拮抗薬ビククリンは、亜鉛と異なりsVRPとともにfPSRも増強した。4.GABA_A受容体拮抗薬ビククリンは、DRPを抑制したが、亜鉛はDRPに影響を与えなかった。5.亜鉛による増強効果は、NMDA受容体拮抗薬ケタミン及びAP-5によって抑制されたが、ATP受容体拮抗薬PPADS及びTNP-ATPは亜鉛の効果に影響を与えなかった。以上の結果から、...
  文部科学省, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 17780215
• Molecular mechanisms of pain signal transmission and evaluation of analgesias inn vitro
  Grants-in-Aid for Scientific Research(基盤研究(B))
  2002 - 2004
  Shigeo ITO; 太田 利男; 乙黒 兼一
  1)Serotonin (5-HT) potentiated Ca^<2+> response to capsaicin in cultured rat dorsal root ganglion (DRG) cells expressing 5-HT_<2A> and 5-HT_7 receptors. The increased response was inhibited by the blocker of protein kinase C or protein kinaseA. 2)In isolated neonatal rat spinal cord, electrical stimulation of the L3 ventral root elicited a fast monosynaptic reflex potential (MSR) followed by very slow potential change (sVRP) in the ipsilateral L3 ventral root. The sVRP was inhibited by α2 adrenoceptor agonists, dexmedetomidine (DEX), xylazine (XY) and clonidine (CLO) or opiate receptor agon...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 14360171
• ラット嗅細胞の匂い応答におけるイオンチャネルと細胞内情報伝達系の関与に関する研究
  研究助成（奨励）
  2003
  乙黒 兼一
  秋山記念生命科学振興財団, Principal investigator, Competitive research funding
• 消化管平滑筋活動における細胞外ATPの役割とその受容体に関する研究
  科学研究費助成事業 特別研究員奨励費
  1998 - 1998
  乙黒 兼一
  日本学術振興会, 特別研究員奨励費, 北海道大学, 97J01042

• モンゴル獣医・畜産分野人材育成能力強化プロジェクト
  2018
  Lecturer, Advisor, Demonstrator
  国際協力機構・モンゴル生命科学大学 獣医学部
• スーパーサイエンスハイスクール
  2012 - 2016
  Lecturer
  北海道釧路湖陵高等学校
  KCS基礎