Pancreatic atrophy in rats produced by the cholecystokinin-A receptor antagonist devazepide

According to recent reports, the powerful and selective cholecystokinin (CCK)-A receptor antagonist devazepide (also referred to as L-364,718 or MK-329) is without effect on the weight of the pancreas. This has been interpreted to mean that basal and meal-stimulated endogenous CCK does not play a major role in the normal maintenance of the pancreas. In the present study we show that continuous subcutaneous infusion of devazepide effectively and dose-dependently reduced the weight of the pancreas both in normal rats and in hyperCCKemic rats (because of pancreaticobiliary diversion). The maximum reduction of the pancreatic weight was 40%. Maximum or near-maximum effects were seen with a dose of 200 micrograms/kg/h. The DNA content of the pancreas was also reduced. The reduction in weight and DNA content of the pancreas was maximal after 10 days. Provided that devazepide acts solely by inhibiting CCK-A receptors, we can conclude that endogenous CCK plays an important role in both normal and stimulated growth of the rat pancreas.