title: Colonic inflammation increases the contribution of muscarinic M2 receptors to carbachol-induced contraction of the rat colon.
abstract: OBJECTIVE
  Carbachol-induced contraction of the rat colon is impaired in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. The main objective of this study was to examine the effect of colitis on the expression and function of muscarinic (M) receptor subtypes in the rat colon.
  
  
  METHODS
  Rats (n = 80) were treated with TNBS and used 5 days later for measurement of contractility, myeloperoxidase activity, histology and expression of muscarinic receptor isoforms using Western blot analysis.
  
  
  RESULTS
  Carbachol produced concentration-dependent contractions of colonic segments from control (n = 40) and TNBS-treated (n = 40) rats with no significant difference in potency. However, the maximum response to carbachol was significantly reduced in colon segments of TNBS-treated rats. The selective muscarinic receptor antagonists 4-diphenylacetoxy-N-methyl piperidine (4-DAMP, M(3)), pirenzepine (M(1)) and methoctramine (M(2)) antagonized carbachol-induced contraction in control (9.1 ± 0.1, 6.7 ± 0.3 and 6.0 ± 0.1, respectively) and TNBS-treated rats (9.2 ± 0.2, 6.9 ± 0.2, 6.7 ± 0.2). The -logK(B) values in control rats are consistent with an action of carbachol on muscarinic M(3) receptors. There was no significant difference in -logK(B) values for 4-DAMP and pirenzepine in control and TNBS-treated rats, but methoctramine was fivefold more potent in TNBS-treated rats, possibly indicating an increased contribution of muscarinic M(2) receptors to carbachol-induced contraction in the inflamed colon. The expression of M(2) receptors was also significantly increased in colon segments from TNBS-treated rats, confirming the increased role of muscarinic M(2) receptors in the inflamed colon.
  
  
  CONCLUSIONS
  The data show that while only M(3) receptors appeared to mediate carbachol-induced contraction in control segments, expression of both M(2) and M(3) receptors was increased in the inflamed rat colon.
authors: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors: Dina M
authors: DM
authors: Jragh
authors: Islam
authors: I
authors: Khan
authors: Mabayoje A
authors: MA
authors: Oriowo
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003092:Colitis / Q000473:pathology; D003106:Colon / Q000473:pathology*; D003959:Diamines / Q000494:pharmacology; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology*; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000187:drug effects*
chemical_list: D003959:Diamines; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D010890:Pirenzepine; D002217:Carbachol; C054938:methoctramine