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Keywords:

  • Ca2+-sensitization;
  • colonic smooth muscle;
  • CPI-17;
  • interleukin-1β;
  • motility disorder;
  • ulcerative colitis

Abstract  The mechanism of gastrointestinal dysmotility in inflammatory bowel disease has not been clarified. In this study, we examined the mechanism involved in the inflamed distal colon isolated from a mouse model of dextran sodium sulphate-induced ulcerative colitis (DSS-treated mouse). Although substance P-induced contraction was not changed, carbachol-induced contraction was reduced in the DSS-treated mouse colon. Pre-incubation with the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) or the cyclooxygenase inhibitor indomethacin did not reverse the carbachol-induced contraction in the DSS-treated mouse colon. In semi-quantitative reverse transcription-polymerase chain reaction experiments and Western blot analysis, muscarinic M3 receptor expressions were not changed. The Ca2+-sensitization of contractile elements induced by carbachol with GTP or GTPγS was reduced in the β-escin-permeabilized DSS-treated mouse colon. Although the expression of proteins such as rhoA, ROCK1, ROCK2 or MYPT1 in smooth muscles was not changed, the expression of CPI-17, the functional protein involved in smooth muscle Ca2+-sensitization, was significantly decreased in the DSS-treated mouse colon. These results suggest that the suppression of carbachol-induced contraction in mice with colitis is attributable at least partially to the increased activity of myosin phosphatase following the downregulation of CPI-17.