Effects of serotonin 5-HT₃ receptor antagonists on CRF-induced abnormal colonic water transport and defecation in rats

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• 作者：Takuya Hirata ; Yoshihiro Keto ; Mari Nakata ; Asako Takeuchi ; Toshiyuki Funatsu ; Shinobu Akuzawa ; Masao Sasamata ; Keiji Miyata
• 关键词：Abnormal defecation ; Colonic water transport ; CRF ; 5-HT₃ receptor antagonist ; (Rat)
• 刊名：European Journal of Pharmacology
• 出版年：2008
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：10 June 2008
• 卷：587
• 期：1-3
• 页码：281-284
• 文件大小：327 K

摘要

The effects of corticotropin releasing factor (CRF) and serotonin (5-HT)₃ receptor antagonists on intestinal water transport are not well understood. Hence, we established a CRF-induced abnormal water transport model in rat colon, and evaluated the effects of 5-HT₃ receptor antagonists including ramosetron, alosetron, and cilansetron, and the antidiarrheal agent loperamide, in this model. In addition, the effects of 5-HT₃ receptor antagonists and loperamide on abnormal defecation induced by CRF in rats were examined. Colonic water transport was measured in colonic loops in conscious rats. Centrally administered CRF (3–30 μg/kg) markedly decreased colonic fluid loss, whereas oral administration of ramosetron (3, 30 μg/kg), alosetron (300 μg/kg), cilansetron (300 μg/kg), or loperamide (3 mg/kg) significantly inhibited it. Ramosetron (1–10 μg/kg), alosetron (10–100 μg/kg), cilansetron (10–100 μg/kg), or loperamide (0.3–3 mg/kg) also showed dose-dependent inhibition of CRF-induced defecation in rats. These results suggest that 5-HT₃ receptors are involved in both abnormal colonic water transport and defecation induced by CRF, and that the inhibitory effects of 5-HT₃ receptor antagonists on CRF-induced abnormal defecation partly result from their ameliorating action on colonic water transport.