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.
Porcher
C
C
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA. christophe.porcher@ujf-grenoble.fr
Horowitz
B
B
Ward
S M
SM
Sanders
K M
KM
D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism*; D009197:Myenteric Plexus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011453:Prostaglandins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011453:Prostaglandins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases