Adenosine A 1 receptor blockade reverses dysmotility induced by ischemia–reperfusion in rat colon

Abstract

This study was designed to assess whether adenosine A 1 receptor antagonists [( R)-1-[( E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] reverse dysmotility induced by ischemia–reperfusion in the rat colon. The gene of adenosine A 1 receptor was expressed in the colon. Clamping (30 min) of the colonic marginal vessels was followed by reperfusion, and the propulsive colonic motility was evaluated. Propulsion was significantly slowed by ischemia–reperfusion, while FK352 and DPCPX abolished this delay. In contrast, the non-selective adenosine receptor antagonist, 8-phenyltheophylline, failed to affect the dysmotility. Thus, adenosine A 1 receptor antagonists have potent therapeutic potential against ischemia–reperfusion-induced dysmotility in the colon.