title: Colonic submucosal 5-HT(3) receptor-mediated somatostatin-dependent secretoinhibitory pathway is suppressed in water-immersion restraint stressed rats.
abstract: 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-HT(3) 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 (I(SC)). Real-time PCR and western blot were performed to study the expression of the 5-HT(3) receptor, 5-HT(4) receptor, and somatostatin receptor 2. Radioimmunoassay was used to measure somatostatin release. After 2h of water-immersion restraint stress, the membrane resistance (Rte) of rat mucosa/submucosa preparations was significantly decreased, but the baseline I(SC) and 5-HT-induced I(SC) responses were significantly increased. The protein expression of the submucosal 5-HT(3) 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-HT(3) 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.
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing (100069), PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.lastname: Hua Guo
authors.forename: Jing-Dong
authors.initials: JD
authors.lastname: Xu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Feng
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Duan
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Zhu
mesh_terms: D000818:Animals; D003106:Colon; D004553:Electric Conductivity; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007101:Immersion; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D012149:Restraint, Physical; D012701:Serotonin / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology; D014326:Tropanes / Q000494:pharmacology; D014867:Water
chemical_list: D044406:Receptors, Serotonin, 5-HT3; D017481:Receptors, Somatostatin; D058831:Serotonin 5-HT3 Receptor Antagonists; D014326:Tropanes; D014867:Water; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D013004:Somatostatin; C042253:bemesetron