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Updated: Aug 11, 2026
Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation
Published on: September 11, 2012
Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation
Koichi Sato1, Hiromichi Ninomiya, Shinsuke Ohkura
1Department of Veterinary Pharmacology, Faculty of Agriculture, University of Yamaguchi, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. k-sato@yamaguchi-u.ac.jp
Abstract:
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). 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). 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. Expression of PAR-2 mRNA in colonic muscularis externa was significantly lower in DSS-treated rats than in control rats. 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.
Insights
Protease-activated receptor-2 (PAR-2) normally relaxes colonic smooth muscle. In an experimental colitis model, this PAR-2 relaxation pathway is suppressed, potentially contributing to inflammatory bowel disease (IBD) motility issues.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pharmacology
Background:
- Protease-activated receptor-2 (PAR-2) is implicated in intestinal inflammation.
- Dysfunctional PAR-2-mediated smooth muscle activity may underlie motility disorders in inflammatory bowel disease (IBD).
Purpose of the Study:
- To investigate the role of PAR-2 in colonic smooth muscle function during experimental colitis.
- To determine if PAR-2 signaling is altered in a rat model of IBD.
Main Methods:
- Assessed trypsin- and peptide-induced relaxation in normal and dextran sodium sulfate (DSS)-inflamed rat colonic smooth muscle.
- Investigated the involvement of specific signaling pathways (apamin, l-NMMA, neuronal blockers).
- Quantified PAR-2 mRNA expression in colonic muscularis externa.
Main Results:
- Trypsin-induced relaxation was impaired in DSS-treated rat colon compared to controls.
- Selective PAR-2 activation with SLIGRL-NH(2) also showed reduced relaxation in inflamed tissue.
- PAR-2 mRNA expression was significantly decreased in DSS-treated rats.
- Small conductance Ca(2+)-activated K(+) channel activation remained unaffected.
Conclusions:
- The PAR-2 mediated relaxation system in colonic smooth muscle is suppressed in this experimental colitis model.
- Reduced PAR-2 function may contribute to the pathogenesis of motility disorders observed in IBD.
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