EFFECTS OF THE CHOLECYSTOKININ RECEPTOR ANTAGONIST L-364,718 ON PANCREATITIS INDUCED BY A DEFICIENT IN CHOLINE AND SUPPLEMENTED WITH ETHIONINE (CDE) DIET IN THE RAT

The role of cholecystokinin (CCK) in the development of a necrotizing acute pancreatitis induced by a diet deficient in choline and suppleme nted with ethionine (CDE) has been evaluated in the rat by using a pot ent CCK receptor antagonist L364,718. Acute pancreatitis was induced b y administration of CDE diet for 14 days. L-364,718 administration was carried out by subcutaneous injections at dose of 0.1 mg/kg/day. panc reatic exocrine secretion (flow, protein, amylase and trypsin outputs) in resting and under infusion of 1.25 mu g/kg/h of CCK-8 were used to evaluate the pancreatic functionality. Others parameters (serum amyla se, percentage fluid in pancreas, haematocrit and mortality) evaluated the severity of pancreatitis. L-364, 718 slightly reduced the mortali ty and the increases of percentage of fluid accumulated in pancreas in CDE diet acute pancreatitis. Basal and CCK stimulated pancreatic secr etion was significantly depressed 36 hours after L-364,718 treatment A slight response to CCK was observed. Nevertheless it was lower than u sually observed in control rats. Our results demonstrate that in the r at chronic L-364,718 treatment did not completely restore pancreatic a ctivity in acute pancreatitis induced by CDE diet Hence CCK cannot be considered as the main factor involved in the development of this panc reatitis model.