Microsomal Prostaglandin E Synthase-1 Plays a Critical Role in Long-term Motility Dysfunction after Bowel Obstruction

Motility dysfunction is present not only during bowel obstruction (BO), but after obstruction is resolved. Previous studies found that lumen distension associated mechano-transcription of COX-2 and production of PGE(2) in gut smooth muscle cells (SMC) account for motility dysfunction during obstruction. We hypothesized that PGE(2) may exert autocrine effect in SMC to induce microsomal prostaglandin E synthase-1 (mPGES-1), which contributes to motility dysfunction after obstruction is resolved. Partial colon obstruction was induced in rats with an obstruction band, which was released 7 days later. Rats were further studied in the post-BO state. Circular muscle contractility of the mid colon (previously distended during obstruction) remained suppressed, and colon transit was impaired in the post-BO state. The COX-2, mPGES-1, and PGE(2) levels were all increased in the distended bowel during obstruction. However, after obstruction was resolved, COX-2 expression returned to normal, whereas mPGES-1 and PGE(2) levels remained increased. Expression of mPGES-1 in colon SMC was inducible by stretch or PGE(2). Administration of mPGES-1 inhibitor Cay 10526 either before or after the release of obstruction normalized PGE(2) levels and improved motility in the post-BO rats. In conclusion, mPGES-1 plays a critical role in the continuous suppression of motor function in the post-BO state.