The anti-CCK effect of glutaramic acid derivatives in anesthetized and conscious rats

The effects of specific gastrin-cholecystokinin (CCK) receptor blockers (proglumide and a new, more potent product of Rotta Research Laboratorium, CR-1392) on pancreatic secretion were studied. Proglumide and CR-1392 caused a rightward and parallel shift, respectively, in the dose-response curve of CCK8 stimulated pancreatic protein secretion in anesthetized rats, demonstrating a competitive-like mechanism of inhibition. The mean PA2 values, demonstrating the 50% inhibitory dose of proglumide and CR-1392 were 3.7 and 5.7, respectively; i.e., CR-1392 proved to be about 100 times more potent than proglumide. In conscious rats, protein output and the volume of pancreatic juice were significantly decreased for about 2 h in response to 150 mg/kg of proglumide or 3 mg/kg of CR-1392 administered s.c. during diversion of pancreatic juice, demonstrating inhibition of endogenous CCK by glutaramic acid derivatives. Indeed, during reintroduction of precollected pancreatic juice into the duodenum, when the release of CCK is known to be almost totally eliminated, pancreatic secretion was not significantly modified by the same doses.