1995 Fiscal Year Final Research Report Summary
Studies on mechanism of drug-induced emesis
| Project/Area Number |
06672274
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
MINAMI Masaru Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido.Professor, 薬学部, 教授 (00142711)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Toru Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences, 薬学部, 助手 (80194041)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Drug-induced emesis / 5-HT_3 antagonist / 5-HT_4 antagonist / Serotonin / Afferent vagal nerve / Enterochromaffin cell / Ferret |
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| Research Abstract |
The increase of afferent vagal nerve activity paralleled the time course of cisplatin-and copper sulfate-increased emesis in ferrets. Ondansetron, serotonin (5-HT)_3 receptor antagonist, and N-3389, both 5-HT_3 and 5-HT_4 receptors antagonist, significantly inhibited the increased vagal nerve activity induced by cisplatin in ferrets and rats. Serotonin and A selective 5-HT_3 receptor agonist, 2-methyl-5-HT,increased the abdominal afferent vagal nerve activity in a dose-dependent manner. A selective 5-HT_4 receptor agonist, 5-methoxytryptamine, also increased the abdominal afferent vagal nerve activity.
We previously reported that cisplatin produced a significant increase in cumulative 5-HT release and that ondansetron did not alter the 5-HT release from the ferret ileum. In this study, 2-methyl-5-HT induced a dose-dependent increase of 5-HT from the rat ileum. This release of 5-HT was significantly reduced by granisetron, a selective 5-HT_3 receptor antagonist. Furthermore, 5-methoxytryptamine induced a concentration-dependent increase of 5-HT in the rat ileum.
These results suggest that both 5-HT_3 and 5-HT_4 receptors may be involved in abdominal afferent vagal nerve activity and intestinal 5-HT release.
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Research Products
(13 results)
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[Publications] Endo, T., Nemoto, M., Monma, Y., Hamaue, N., Togashi, M.and Hirafuji, M.: "Combined effect of domperidone and granisetron on cisplatin-induced emesis in the ferret" Oyo Yakuri/Pharmacometrics. 47. 435-442 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Endo, T., Nemoto, M., Minami, M., Yoshioka, M., Saito, H.and Parvez, S.H.: "Changes in the afferent abdominal vagl nerve activity induced by cisplatin and copper sulfate in the ferret" Biogenic Amines. 11. 399-407 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Minami, M., Tamakai, H., Ogawa, T., Endo, T., Hamaue, N., Hirafuji, M., Yoshioka, M.and Blower, P.R.: "Chemical modulation of 5-HT_3 and 5-HT_4 receptors affects the release of 5-hydroxytryptamine from the ferret and rat intestine" Res.Commun.Pathol.Pharmacol.89. 131-142 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Minami, M., Endo, T., Nemoto, M., Hamaue, N., Hirafuji, M., Monma, Y., Yajima, T., Yoshioka, M.and Saito, H.: "How do toxic emetic stimuli cause serotonin release in the gut and the brain?" Proceeding of 2nd International Symposium "Serotonin and the control of emesis : a decade of progress? ". (in press).
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「研究成果報告書概要(欧文)」より
