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 N(G)-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 GTPgammaS was reduced in the beta-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.

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‐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. 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. British Journal of Pharmacology (2006) 148, 200–207. doi:

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Abstract-The role of glycolysis in the tension development under anoxic conditions in a high-K medium was studied in the intestinal smooth muscle of guinea pig taenia coll. After exposure to the high-K medium (isotonic , 60 mM) under normal oxygen for 30 min , the muscles were exposed to a high-K medium bubbled with N2 gas . The tonic contraction decreased gradually to about 10% of the original level. Glucose was then cumulatively added to the high-K medium under anoxia.

ABSTRACT. Intestinal muscularis resident macrophages distributed in myenteric region may play an important role in the immunological host defense against infection. In this study, we investigated the phagocytic stimulation of resident macrophages on cyclooxygenase-2 (COX-2) expression and smooth muscle contraction in the small intestine of rat. After the injection of FITC-dextran to rat, phagocytosed macrophages could be detected in the myenteric plexus. FITC-positive macrophages were also immunostained with COX-2 antibody. The number of COX-2 immunopositive cells increased in a time-dependent manner reaching its maximum at 4 hr after the injection, which then decreased gradually but considerable number of cells were still remained on 7 days. The injection of FITC-dextran, however, did not change the population of ED2-positive resident macrophages even on 7 days. Production of PGE 2 was significantly higher in the dextran treated tissue as compared to control tissue. In the smooth muscle tissue phagocytosed dextran, carbachol-induced contraction was significantly decreased. The suppression of the carbachol-induced contraction was completely restored by COX inhibitor, indomethacin. Finally we demonstrated that, in freshly isolated macrophage cells, addition of dextran induced a slow and sustained increase in intracellular Ca 2+ concentration. These results indicate that phagocytotic activation of muscularis resident macrophages induces COX-2 gene expression and then results in production of PGE 2 to suppress the smooth muscle contractile activity. KEY WORDS: intestinal smooth muscle, phagocytosis, prostaglandin, resident macrophage.