The effect of the CCK receptor antagonist CR 1409 on bile reflux pancreatitis in the opossum.
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.
Larsen
F
F
Department of Surgery, St. Louis University Medical Center, Missouri 63110-0250.
Schlarman
D
D
Andrus
C C
CC
Kaminski
D L
DL
D000681:Amylases / Q000097:blood; D000818:Animals; D001655:Bile Reflux / Q000150:complications*; D002766:Cholecystokinin / Q000097:blood; D003135:Common Bile Duct / Q000601:surgery; D005260:Female; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D008026:Ligation; D008297:Male; D009893:Opossums; D009929:Organ Size; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D007328:Insulin; D011949:Receptors, Cholecystokinin; D005934:Glucagon; D002766:Cholecystokinin; D000681:Amylases; D011377:Proglumide; C048181:lorglumide