title: A new class of potent gastrin antagonists.
abstract: The hexapeptide Z-Tyr(SO-3)-Met-Gly-Trp-Met-Asp-NH2, 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, (ED50 = 1.5 mumol . kg-1), without agonist activity. Desulfation of the tyrosine residue slightly altered this effect. The tripeptide Boc-Trp-Met-Asp-NH2 showed similar effects, but had lower potency (ED50 = 12 mumol . 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.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology* / Q000031:analogs & derivatives; D005750:Gastric Juice / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011949:Receptors, Cholecystokinin; D013329:Structure-Activity Relationship
chemical_list: D005755:Gastrins; D009842:Oligopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; C038242:cholecystokinin (27-32)-amide; D002766:Cholecystokinin