title: The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats.
abstract: BACKGROUND
  The mechanism underlying chronic stress-induced gastrointestinal (GI) dysmotility has not been fully elucidated and GI hormones have been indicated playing a role in mediating stress-induced changes in GI motor function.
  
  
  OBJECTIVE
  Our objective was to study the possible role of substance P (SP) in the colonic hypermotility induced by repeated water avoidance stress (WAS) which mimics irritable bowel syndrome.
  
  
  METHODS
  Male Wistar rats were submitted to WAS or sham WAS (SWAS) (1h/day) for up to 10 consecutive days. Enzyme Immunoassay Kit was used to detect the serum level of SP. The expression of neurokinin-1 receptor (NK1R) was investigated by Immunohistochemistry and Western blotting. The spontaneous contraction of muscle strip was studied in an organ bath system. L-type calcium channel currents (ICa,L) of smooth muscle cells (SMCs) were recorded by whole-cell patch-clamp technique.
  
  
  RESULTS
  Fecal pellet expulsion and spontaneous contraction of proximal colon in rats were increased after repeated WAS. The serum level of SP was elevated following WAS. Immunohistochemistry proved the expression of NK1R in mucosa, muscularis and myenteric plexus. Western blotting demonstrated stress-induced up-regulation of NK1R in colon devoid of mucosa and submucosa. Repeated WAS increased the contractile activities of longitudinal muscle and circular muscle strips induced by SP and this effect was reversed by a selective NK1R antagonist. The ICa,L of SMCs in the WAS rats were drastically increased compared to controls after addition of SP.
  
  
  CONCLUSIONS
  Increased serum SP level and up-regulated NK1R in colon may contribute to stress-induced colonic hypermotility. And L-type calcium channels play a potentially important role in the process of WAS-induced dysmotility.
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors: Ping
authors: P
authors: Lu
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China. Electronic address: xhnklhs@163.com.
authors: Hesheng
authors: H
authors: Luo
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors: Xiaojing
authors: X
authors: Quan
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors: Han
authors: H
authors: Fan
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors: Qincai
authors: Q
authors: Tang
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors: Guang
authors: G
authors: Yu
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors: Wei
authors: W
authors: Chen
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.
authors: Hong
authors: H
authors: Xia
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000503:physiopathology*; D005769:Gastrointestinal Motility; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology; D009197:Myenteric Plexus / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D013373:Substance P / Q000097:blood*
chemical_list: D020746:Calcium Channels, L-Type; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013373:Substance P
keywords: Motility; Patch-clamp technique; Rat; Stress; Substance P