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Impairment of PAR‐2‐mediated relaxation system in colonic smooth muscle after intestinal inflammation
Author(s) -
Sato Koichi,
Ninomiya Hiromichi,
Ohkura Shinsuke,
Ozaki Hiroshi,
Nasu Tetsuyuki
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706717
Subject(s) - apamin , endocrinology , medicine , motility , tetrodotoxin , chemistry , hexamethonium , carbachol , propranolol , colitis , inflammation , stimulation , potassium channel , biology , microbiology and biotechnology
1 Protease‐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). 2 Stimulation 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). 3 In colon inflamed by dextran sodium sulphate (DSS), trypsin‐induced inhibitory effects were significantly reduced. Relaxation induced by SLIGRL‐NH 2 , 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 Ca 2+ ‐activated K + channel, were unaffected. 4 Expression of PAR‐2 mRNA in colonic muscularis externa was significantly lower in DSS‐treated rats than in control rats. 5 These 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