Proglumide and benzotript: members of a different class of cholecystokinin receptor antagonists

In dispersed acini from guinea pig pancreas, proglumide (DL-4-benzamido-N, N-dipropylglutaramic acid) and benzotript (N-p-chlorobenzoyl-L-tryptophan) caused a rightward shift in the dose--response curve for cholecystokinin-stimulated amylase secretion but did not alter the maximal increase in amylase secretion caused by cholecystokinin. At relatively low concentrations, proglumide did not alter the stimulation of enzyme secretion caused by secretagogues whose effects are mediated by adenosine 3'5'-monophosphate (e.g., vasoactive intestinal peptide or secretin) and did not alter the stimulation of enzyme secretion caused by secretagogues that have a mode of action similar to that of cholecystokinin but act through different receptors (e.g., bombesin, physalaemin, eledoisin, and ionophore A23187). There was a close correlation between the ability of proglumide or benzotript to inhibit binding of 125I-labeled cholecystokinin to its receptors on pancreatic acini and the abilities of these compounds to inhibit the action of cholecystokinin on enzyme secretion and on calcium outflux. These results indicate that proglumide and benzotript are members of a different class of cholecystokinin receptor antagonists.