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

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 mu g/kg) markedly decreased colonic fluid loss, whereas oral administration of ramosetron (3, 30 mu g/kg), alosetron (300 mu g/kg), cilansetron (300 mu g/kg), or loperamide (3 mg/kg) significantly inhibited it. Ramosetron (1-10 mu g/kg), alosetron (10-100 mu g/kg), cilansetron (10-100 mu g/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. (C) 2008 Elsevier B.V. All rights reserved.