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Constitutive and functional expression of cyclooxygenase 2 in the murine proximal colon
Author(s) -
Porcher C.,
Horowitz B.,
Ward S. M.,
Sanders K. M.
Publication year - 2004
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2004.00568.x
Subject(s) - cyclooxygenase , interstitial cell of cajal , immunohistochemistry , tunica , gene isoform , medicine , endocrinology , knockout mouse , receptor , chemistry , biology , enzyme , anatomy , biochemistry , gene
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.