5-HT-Induced, 5-HT_3 Receptor-Mediated, and Ruthenium Red- and Capsaicin-Sensitive Positive Chronotropic Effects in the Isolated Guinea Pig Atrium
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概要
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We investigated the mechanisms of 5-HT-induced tachycardia, which we reported previously to be triggered by 5-HT3 receptor stimulation, in the isolated guinea pig atrium in comparison with that induced by isoproterenol and histamine. We found that 5-HT-induced tachycardia was completely inhibited by ruthenium red. 5-HT-induced tachycardia was reduced in the capsaicin pre-treated atrium as well as in the presence of capsaicin. The effects of isoproterenol and histamine were not affected by ruthenium red or capsaicin treatment. Furthermore, 5-HT-induced tachycardia was found to be potentiated by thiorphan, an inhibitor of peptide degeneration. Calcitonin gene-related peptide (CGRP) (1 – 37), a full agonist of CGRP1-like receptors, was found to act selectively as a potent stimulator of chronotropic action. CGRP (8 – 37), an antagonist of CGRP1-type receptors, inhibited 5-HT-induced tachycardia as well as effects induced by CGRP (1 – 37). The observation that tetrodotoxin failed to affect 5-HT-induced tachycardia excluded the involvement of 5-hydroxytryptaminergic interneurons. Thus, we confirmed that the mechanism of 5-HT-induced tachycardia is distinct from that induced by isoproterenol and histamine. In conclusion, the activation of 5-HT3 receptors on the sensory nerve terminals brought about ruthenium red-sensitive Ca2+ influx and resulted in the release of CGRP from capsaicin-sensitive stores, and then CGRP stimulated CGRP1-like receptors to produce 5-HT-induced tachycardia.
- 社団法人 日本薬理学会の論文
- 2002-07-01
著者
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Nakata Yoshihiro
Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Japan
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Nishio Hiroaki
Department Of Molecular Pharmacology Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama Univer
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WATANABE Tomoko
Department of Applied Chemistry, Faculty of Engineering, Utsunomiya University
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Nishio H
Department Of Pharmacology Faculty Of Pharmacy & Pharmaceutical Sciences Fukuyama University
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MORIMOTO Yukiko
Department of Pharmacology, Institute of Pharmaceutical Sciences, Hiroshima University School of Med
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HISAOKA Kazue
Department of Pharmacology, Institute of Pharmaceutical Sciences, Hiroshima University School of Med
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Hisaoka Kazue
Department Of Pharmacology Institute Of Pharmaceutical Sciences Hiroshima University School Of Medic
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Morimoto Yukiko
Department Of Pharmacology Institute Of Pharmaceutical Sciences Hiroshima University School Of Medic
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Morimoto Yukiko
Department Of
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Nakata Yoshihiro
Department Of Biophysics Gunma University
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Nakata Yoshihiro
Department Of Pharmacology Institute Of Pharmaceutical Sciences Hiroshima University School Of Medic
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Watanabe Tomoko
Department Of Pharmacology Faculty Of Pharmacy & Pharmaceutical Sciences Fukuyama University
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Watanabe Tomoko
Department Of Applied Chemistry Faculty Of Engineering Utsunomiya University
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