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 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.