Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation

Authors

  • Koichi Sato,

    Corresponding author
    1. Department of Veterinary Pharmacology, Faculty of Agriculture, University of Yamaguchi, 1677-1 Yoshida, Yamaguchi 753-8515, Japan
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  • Hiromichi Ninomiya,

    1. Department of Veterinary Pharmacology, Faculty of Agriculture, University of Yamaguchi, 1677-1 Yoshida, Yamaguchi 753-8515, Japan
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  • Shinsuke Ohkura,

    1. Department of Veterinary Pharmacology, Faculty of Agriculture, University of Yamaguchi, 1677-1 Yoshida, Yamaguchi 753-8515, Japan
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  • Hiroshi Ozaki,

    1. Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
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  • Tetsuyuki Nasu

    1. Department of Veterinary Pharmacology, Faculty of Agriculture, University of Yamaguchi, 1677-1 Yoshida, Yamaguchi 753-8515, Japan
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Department of Veterinary Pharmacology, Faculty of Agriculture, University of Yamaguchi, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. E-mail: k-sato@yamaguchi-u.ac.jp

Abstract

  • 1Protease-activated receptor (PAR)-2 plays important roles in intestinal inflammatory responses. Changes in PAR-2-mediated smooth muscle function may contribute pathophysiologically to the intestinal motility disorders often observed in inflammatory bowel disease (IBD).
  • 2Stimulation of PAR-2 by trypsin-induced relaxation of carbachol- and KCl-induced contractions in normal rat colonic smooth muscle was completely resolved by tissue pretreatment with apamin, but not by pretreatment with l-NMMA or a cocktail of neuronal blockers (tetrodotoxin, hexamethonium and propranolol).
  • 3In colon inflamed by dextran sodium sulphate (DSS), trypsin-induced inhibitory effects were significantly reduced. Relaxation induced by SLIGRL-NH2, a selective PAR-2-activating peptide, was also reduced in DSS-treated rat colon. However, inhibitory effects of 1-ethylbenzimidazolin-2-one, an activator of small conductance Ca2+-activated K+ channel, were unaffected.
  • 4Expression of PAR-2 mRNA in colonic muscularis externa was significantly lower in DSS-treated rats than in control rats.
  • 5These results suggest that the PAR-2 mediated relaxation system in colonic smooth muscle is suppressed in this experimental colitis rat model, and may contribute to motility disorders in IBD.

British Journal of Pharmacology (2006) 148, 200–207. doi:10.1038/sj.bjp.0706717

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