THERAPEUTIC AND PROTECTIVE EFFECT OF SUBCUTANEOUS INJECTIONS OF L-364,718 ON CERULEIN-INDUCED ACUTE-PANCREATITIS

The prophylactic and therapeutic effects of a potent cholecystokinin ( CCK) receptor antagonist, L-364,718, on acute pancreatitis induced by caerulein were evaluated, analyzing morphologic and functional pancrea tic parameters jointly. Edematous pancreatitis was induced by four sub cutaneous injections of caerulein (20 mug/kg) in rats at 1-h intervals . Prophylactic administration of L-364,718 (0.1 mg/kg) prevented rise in serum amylase levels, interstitial edema, vacuolization, and impair ment of pancreatic enzyme secretion that accompany caerulein-induced a cute pancreatitis. After 7 days, a spontaneous regression of the morph ologic alterations caused by caerulein-induced acute pancreatitis occu rs; however, recovery of the secretory function of the pancreas was on ly reached after this period of time when L-364,718 was administered t herapeutically (0.1 mg/kg/day). Prophylactically or therapeutically ad ministered, L-364,718 exerts a beneficial effect on caerulein-induced acute pancreatitis, indicating that CCK (exogenous or endogenous) play s an important role in the development of this pathology.