Pulmonary, Gastrointestinal and Urogenital PharmacologyColonic submucosal 5-HT3 receptor-mediated somatostatin-dependent secretoinhibitory pathway is suppressed in water-immersion restraint stressed rats

We have demonstrated that the activation of 5-hydroxytryptamine (5-HT) receptor 3 in the submucosal plexus suppresses 5-HT-induced colonic ion secretion by increasing submucosal somatostatin release. A number of psychological and physical stresses have impacts on the intestinal mucosal functions, including secretion and the epithelial barrier. Whether the 5-HT3 receptor-mediated somatostatin-dependent secretoinhibitory pathway in the rat distal colon is involved in the stress process is still unknown. The present study aims to investigate the effect of the water-immersion restraint stress on this inhibitory pathway and its underlying mechanisms. Mucosa/submucosa preparations from the rat distal colon were mounted in the Ussing chambers for the measurement of short-circuit current (ISC). Real-time PCR and western blot were performed to study the expression of the 5-HT3 receptor, 5-HT4 receptor, and somatostatin receptor 2. Radioimmunoassay was used to measure somatostatin release. After 2 h of water-immersion restraint stress, the membrane resistance (Rte) of rat mucosa/submucosa preparations was significantly decreased, but the baseline ISC and 5-HT-induced ISC responses were significantly increased. The protein expression of the submucosal 5-HT3 receptors and mucosal somatostatin receptor 2 were down-regulated, and the 5-HT-induced somatostatin release from the mucosa/submucosa preparations was significantly reduced in the stress group. Taken together, these results suggest that the 5-HT3 receptor-mediated somatostatin-dependent secretoinhibitory pathway is suppressed in the water-immersion restraint stressed rats, which may contribute to the acute stress-induced increase in colonic secretion.