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

Abstract

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 secretagogs whose effects are mediated by AMP (e.g., vasoactive intestinal peptide or secretin) and did not alter the stimulation of enzyme secretion caused by secretagogs that have a mode of action similar to that of cholecystokinin but act through different receptors (e.g., bombesin, physalaemin, eledoisin and ionophore A23187 [calcimycin]). 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 Ca outflux. Proglumide and benzotript are members of a different class of cholecystokinin receptor antagonists.