Constitutive and functional expression of cyclooxygenase 2 in the murine proximal colon.

Recent reports suggest that cyclo-oxygenase (COX)-2, an inducible COX isoform may be constitutively expressed in gastrointestinal tissues. This study has evaluated the expression and function of COX-2 in the tunica muscularis of the murine proximal colon. Cyclo-oxygenase-2-like (COX-2-LI) immunoreactivity was found in a subpopulation of neurones in the myenteric and submucosal ganglia and in interstitial cells of Cajal within the muscle layers (IC-IM). Reverse transcriptase polymerase chain reaction (RT-PCR) verified expression of COX-2 in colonic muscles, and quantitative PCR demonstrated that COX-1 transcriptional expression was greater than COX-2. To test the functional significance of COX-2 expression, the effects of a COX-2 inhibitor were compared with the effects of indomethacin (COX-1/COX-2 inhibitor) on circular muscle contractions. The experiments indicate that indomethacin and the specific COX-2 inhibitor, GR253035X, increased the amplitude of phasic contractions, suggesting production of inhibitory prostaglandins tonically dampen contractile activity. The effects of indomethacin were reduced when tested on phasic contractions of muscles from COX-2 knockout mice. GR253035X did not affect contractions in muscles of COX-2 knockout animals. These studies demonstrate constitutive expression of COX-2 in the tunica muscularis of the proximal colon. The COX-2 appears to contribute a significant amount of the prostaglandins that affect the contractile behaviour of colonic muscles.