Endo T, Ogawa T, Hamaue N, Akita K, Hirafuji M, Minami M, Blower P R
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Res Commun Mol Pathol Pharmacol. 1998 Jun;100(3):243-53.
We investigated the influence of granisetron, a 5-HT3 receptor antagonist, on the increase in 5-hydroxytryptamine (5-HT) release induced by cisplatin from the isolated ileum of the ferret, a species known to vomit in response to cisplatin. 2-Methyl-5-HT, a selective 5-HT3 receptor agonist, increased the release of 5-HT from the ferret ileum in a concentration-dependent manner within the range of 10(-7) to 10(-6)M. The 5-HT release induced by 2-methyl-5-HT was significantly inhibited by a concomitant perfusion with granisetron (10(-6)M). Cisplatin also increased the 5-HT release from the ferret ileum within the range of 10(-8) to 10(-6)M, in a concentration-dependent manner. Granisetron (10(-6)M) also significantly inhibited the cisplatin-induced 5-HT release. Since the cisplatin-induced 5-HT release was significantly inhibited by tetrodotoxin, the possible involvement of an interneuron pathway in the cisplatin-induced 5-HT release mechanism was suggested in the ileal tissue. It is likely that granisetron inhibited the cisplatin-induced 5-HT release from the gut EC cells by producing blockade of an EC cell 5-HT3 receptor.
我们研究了5 - 羟色胺（5 - HT）3受体拮抗剂格拉司琼对顺铂诱导的雪貂离体回肠5 - 羟色胺（5 - HT）释放增加的影响，雪貂是一种已知会对顺铂产生呕吐反应的物种。选择性5 - HT3受体激动剂2 - 甲基 - 5 - HT在10（-7）至10（-6）M范围内以浓度依赖的方式增加了雪貂回肠5 - HT的释放。与格拉司琼（10（-6）M）同时灌注可显著抑制2 - 甲基 - 5 - HT诱导的5 - HT释放。顺铂在10（-8）至10（-6）M范围内也以浓度依赖的方式增加了雪貂回肠5 - HT的释放。格拉司琼（10（-6）M）也显著抑制了顺铂诱导的5 - HT释放。由于顺铂诱导的5 - HT释放被河豚毒素显著抑制，提示在回肠组织中可能有中间神经元途径参与顺铂诱导的5 - HT释放机制。格拉司琼可能通过阻断肠嗜铬（EC）细胞的5 - HT3受体来抑制顺铂诱导的肠道EC细胞5 - HT释放。
