OCTREOTIDE AND CHOLECYSTOKININ ANTAGONIST REDUCE EDEMA IN OBSTRUCTION-INDUCED ACUTE-PANCREATITIS

Obstruction-induced acute pancreatitis in rats is associated with incr eased plasma cholecystokinin (CCK) levels. Duodenal replacement of bil e reduces severity of pancreatitis and limits CCK increase. We investi gated the role of CCK in the pathogenesis of obstruction-induced acute pancreatitis by pretreating rats with the somatostatin analog octreot ide and the CCK antagonist L-364,718. Octreotide inhibits duodenal CCK release, and L-364,718 competitively blocks CCK receptors. We studied 31 rats after (1) sham operation (n = 7), (2) bile and pancreatic duc t obstruction (BPDO) (n = 12), (3) BPDO plus octreotide (20 mug/kg IP and then 5 mug/kg/hr IV) (n = 6), and (4) BPDO plus L-364,718 (1 mg/kg (IP)and then 0.25 mg/kg/hr IV) (n = 6). Rats were killed after 18 hou rs. Pancreas weight, acute pancreatitis histology score, and plasma am ylase and CCK levels were determined. Octreotide and L-364,718 limited the increase in pancreas weight. Octreotide also limited the rise in plasma CCK levels. These findings suggest that CCK may play a role in the pathogenesis of obstruction-induced acute pancreatitis.