Effect of opiates on human colonic adenylate cyclase activity

To elucidate a possible mechanism whereby opiates affect human intestinal fluid secretion, opiate effects on human basal and stimulated colonic adenylate cyclase activity were determined. Morphine (10 microM) and naloxone (1 microM) did not affect basal colonic adenylate cyclase activity: 32.6 +/- 2.6 (n = 23; X +/- S.E.) pmol cAMP/mg protein per 10 min or its stimulation induced by sodium fluoride or VIP. However, morphine inhibited the stimulation induced by prostaglandin E2, an effect which was blocked by naloxone. Synthetic enkephalins and metabolically stable retro inverso enkephalins also prevented PGE2-induced stimulation of colonic adenylate cyclase activity. The addition of calcium (0.1 mM) decreased the basal and PGE2-stimulated enzyme activities by 35% and 50%, respectively, regardless of the presence or absence of morphine. These results suggest that morphine and synthetic enkephalins do not affect basal human colonic adenylate cyclase activity but inhibit its stimulation induced by PGE2. This effect may be one of the mechanisms whereby opiates affect intestinal fluid transport.