title: A synthetic peptide derivative that is a cholecystokinin receptor antagonist.
abstract: So far, there are no known peptidic effective receptor antagonists of both peripheral and central effects of cholecystokinin (CCK). Here, we describe a synthetic peptide derivative of CCK, t-butyloxycarbonyl-Tyr(SO3-)-Met-Gly-D-Trp-Nle-Asp 2-phenylethyl ester 1 (where Nle is norleucine), which is a potent CCK receptor antagonist. In rat and guinea pig dispersed pancreatic acini, this peptide derivative did not alter amylase secretion, but was able to antagonize the stimulation caused by cholecystokinin-related agonists. It caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion with half-maximal inhibition of CCK-8-stimulated amylase release at a concentration of about 0.1 microM. Compound 1 was able to inhibit the binding of labeled CCK-9 (the C-terminal nonapeptide of CCK) to rat and guinea pig pancreatic acini (IC50 = 5 X 10(-8) M) as well as to guinea pig cerebral cortical membranes (IC50 = 5 X 10(-7) M). These results indicate that Compound 1 is a potent competitive CCK receptor antagonist.
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D011949:Receptors, Cholecystokinin; C052607:t-butyloxycarbonyl-(sulfo-Tyr)-Met-Gly-Trp-Nle-Asp 2-phenylethyl ester; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide