A new class of potent gastrin antagonists

Abstract The hexapeptide Z-Tyr(SO 3 − )-Met-Gly-Trp-Met-Asp-NH 2 , from the natural sequence of C-terminal cholecystokinin was found to be a competitive antagonist of cholecystokinin receptors, in vitro. In the present study, we report that this peptide inhibits gastrin-induced acid secretion in vivo, (ED 50 = 1.5 μ mol · kg −1 ), without agonist activity. Desulfation of the tyrosine residue slightly altered this effect. The tripeptide Boc-Trp-Met-Asp-NH 2 showed similar effects, but had lower potency (ED 50 = 12 μ mol · kg −1 ). From these preliminary results, it can be concluded that removal of the phenylalanine residue from the C-terminal sequence of CCK or gastrin, leads to an antagonist of the natural hormones and that C-terminal phenylalanine residue is important for agonist activity. As compared with proglumide, a well known gastrin receptor antagonist, these peptides were 20–200 times more potent as inhibitors on the same model.