1996 Fiscal Year Final Research Report Summary
Studies on mechanism of exocytosis of serotonin from enterochromaffin cell
| Project/Area Number |
07557316
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences |
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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, 講師 (80194041)
HIRAFUJI Masahiko Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences, 薬学部, 助教授 (20142987)
YAJIMA Toshihiko Department of Anatomy, School of Dentistry, Health Sciences University of Hokkai, 歯学部, 教授 (10018749)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Drug-induced emesis / Serotonin / 5-HT3-receptor / Enterochromaffin cell / Ferret |
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| Research Abstract |
In this study, a selective serotonin (5-HT)_3 receptor agonist, 2-methyl-5-HT induced a concentration-dependent increase of 5-HT release from the ileum in ferrets and rats. A selective 5-HT_4 receptor agonist, 5-methoxytryptamine, also produced a concentration-dependent increase of 5-HT release in the ileum of ferrets and rats. Granisetron, a selective 5-HT_3 receptor antagonist, inhibited the increased 5-HT release from the ileum induced by 2-methyl-5-HT in ferrets and rats. Cisplatin produced an increase in 5-HT release from ferret ileum. Granisetron inhibited the cisplatin-induced 5-HT release from ferret ileurm. The increase of 5-HT release from ileum paralleled the time course of cisplatin-induced emesis in ferrets. Ouabain produced a dose-related emetic response in the ferret. Ouaba in produced an increase in 5-HT release from ferret ileum and increased the abdominal afferent vagal nerve activity in ferrets. Granisetron inhibited the ouabain-induced 5-HT release from the ferret ileum and the increased nerve activity in ferrets.in order to investigate the precise mechanism of 5-HT release from enterochromaffin (EC) cells, attempts were made to establish the method to isolate mouse ileal crypts, and to measure the intracellular calcium concentration in crypt cells including epithelial cells and EC cells. We observed that ATP, carbachol and norepinephrine induced the intracellular calcium mobilization in crypt cells. The identification of EC cells and the modulation of intracellular calcium mobilization by 5-HT-related compounds are next subject. Thus, this study indicated that 5-HT release from EC cells was closely related to emetic response induced by ouabain and anti-cancer drugs such as cisplatin. 5-HT receptor subtypes in EC cells and/or intemeurons in the ileal tissue seem to be involved in the mechanism of 5-HT release. Further study using ileal crypts isolated from ferrets is required.
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[Publications] Endo, T., Nemoto, M., Minami, M., Yoshioka, M., Saito, H.and Parvez, S.H.: "Changes in the afferent abdominal vagal 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., Tamakai, H., Ogawa, T., Hamaue, N., Hirafuji, M., Monma, Y., Yoshioka, M.and Hagihara, K.: "Antiemetic effect of N-3389, a newly synthesized 5-HT_3 and 5-HT_4 receptor antagonist, in ferrets." Eur.J.Pharmacol.321. 333-342 (1997)
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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? "Serotonin and the scientific basis of anti-emetic therapy" ed.by Reynolds, D.J.M., Andrews, P.L.R.and Devis, C.J.Oxford Clinical Communications, Oxford, 68-76 (1995)
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「研究成果報告書概要(欧文)」より
