Availability of specific
cholecystokinin (
CCK) receptor antagonists has the potential for contributing to delineation of the role of CCK in the development of
pancreatitis and, perhaps, development of new therapeutic agents for treatment of the disorder. The purpose of this study was to evaluate the effect of a potent
CCK receptor antagonist,
CR 1409, on
bile reflux pancreatitis. The opossum pancreatic duct enters the common duct in such a position that it is possible to ligate the common duct distal to the pancreatic duct, resulting in bile refluxing into the pancreatic duct and producing
pancreatitis.
CR 1409 was administered to opossums at the time of distal common duct
ligation and at the time of cystic- and common ducts
ligations. In a separate group,
CR 1409 administration was begun 24 hours following onset of
pancreatitis. Control experiments were performed, in which
CR-1409 was not administered. Serum
amylase, pancreas gland weights,
inflammation, and systemic venous
insulin,
glucagon, and CCK concentrations were evaluated. Bile duct
ligation resulted in significant
hyperamylasemia, pancreas gland
edema,
inflammation, hyperglucagonemia, hypercholecystokinemia, and hypoinsulinemia.
CR 1409, administered at the onset of
pancreatitis, significantly decreased
amylase concentrations, gland weight, and
inflammation, when compared to control values. Hormonal changes associated with
pancreatitis were also significantly altered by
CR 1409 administration. When administered 24 hours following onset of
pancreatitis,
CR 1409 was not effective in altering the
pancreatitis produced by bile duct
ligation. The results suggest that CCK plays a permissive or contributory role in the inflammatory process and in associated hormonal changes during development of
bile reflux pancreatitis in the opossum.