EFFECTS OF A NEW CHOLECYSTOKININ ANTAGONIST, TS-941, ON EXPERIMENTAL ACUTE-PANCREATITIS IN RATS

The effects of a new benzodiazepine-derivative, cholecystokinin recept or antagonist, TS-941, on experimental acute pancreatitis were studied in rats. Hemorrhagic pancreatitis was induced by an infusion of a mix ture of trypsin and taurocholate into the pancreatic duct. Edematous p ancreatitis was induced by intraperitoneal injection of 40 mu g/kg bod y weight of cerulein at 0 and 1 h after the start of the experiment. T S-941 (3 mg/kg) was injected subcutaneously immediately and 3 h after the induction of pancreatitis. In trypsin-taurocholate-induced pancrea titis, TS-941, with or without the synthetic trypsin inhibitor ONO-340 3, had no beneficial effects on the survival rate, pancreatic wet weig ht, and serum pancreatic enzymes. In cerulein-induced pancreatitis, th e treatment with TS-941 significantly reduced the increases of pancrea tic wet weight and serum amylase and lipase. Plasma trypsinogen activa tion peptide (TAP) significantly rose 1 h after the first injection of cerulein. TS-941 inhibited the liberation of TAP in cerulein-induced pancreatitis. These results show that TS-941 is effective for preventi on of cerulein-induced edematous pancreatitis. ONO-3403 has beneficial effects on trypsin-taurocholate-induced hemorrhagic pancreatitis, but the combination of TS-941 and ONO-3403 has no additive effect.