| 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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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Drug-induced emesis / 5-HT_3 antagonist / 5-HT_4 antagonist / Serotonin / Afferent vagal nerve / Enterochromaffin cell / Ferret / 5-HT_<>拮抗薬 |
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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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