Failure of a potent cholecystokinin antagonist to protect against diet-induced pancreatitis in mice.
The effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on two forms of experimental acute pancreatitis in mice were evaluated. The antagonist prevented the hyperamylasemia, pancreatic edema, and acinar cell vacuolization that followed administration of a supramaximally stimulating dose of the cholecystokinin analogue cerulein. In contrast, the same dose of L-364,718 (1 mg/kg/6 h) and an even higher dose (10 mg/kg/6 h) failed to prevent the hyperamylasemia, acinar cell necrosis, and mortality that followed administration of a choline-deficient ethionine-supplemented diet. These observations are at variance with those previously reported to follow administration of the relatively weak cholecystokinin antagonist proglumide (Niederau C et al. J Clin Invest 1986;78:1056-63). The observations reported in this communication suggest that cholecystokinin does not play an important role in diet-induced pancreatitis and that CCK receptor antagonists are unlikely to be of benefit in the treatment of clinical acute pancreatitis.
Ohshio
G
G
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215.
Saluja
A
A
Leli
U
U
Sengupta
A
A
Steer
M L
ML
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002108:Ceruletide; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D002796:Choline Deficiency; D020109:Devazepide; D004032:Diet / Q000009:adverse effects*; D005001:Ethionine / Q000494:pharmacology; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D010195:Pancreatitis / Q000209:etiology / Q000517:prevention & control*
D001570:Benzodiazepinones; D002108:Ceruletide; D002766:Cholecystokinin; D020109:Devazepide; D005001:Ethionine