title: A pseudopeptide that is a potent cholecystokinin agonist in the peripheral system is able to inhibit the dopamine-like effects of cholecystokinin in the striatum.
abstract: There are no known specific effective cholecystokinin (CCK) receptor antagonists of both peripheral and central nervous systems. Here, we describe experiments which demonstrate that a synthetic pseudopeptide analogue of CCK-7 is a potent agonist in the peripheral system and behaves as a selective and highly potent inhibitor of the dopamine-like effects of CCK in the striatum. This compound, t-butyloxycarbonyl-Tyr (SO3H)-Nle psi (COCH2)Gly-Trp-Nle-Asp-Phe-NH2, is able to stimulate enzyme secretion from rat pancreatic acini, with high efficacy and potency. It is also very potent in inhibiting the binding of labeled CCK-8 to rat pancreatic acini (IC50 = 5 nM) and to guinea pig and mouse brain membranes (IC50 = 0.7 nM). However, this compound is able to antagonize the effects of intrastriatally injected t-butyloxycarbonyl-[Nle28,31] CCK-8 in mice, with high potency.
authors.affiliation: Centre de Pharmacologie-Endocrinologie, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Mendre
authors.forename: M
authors.initials: M
authors.lastname: Rodriquez
authors.forename: C
authors.initials: C
authors.lastname: Gueudet
authors.forename: M F
authors.initials: MF
authors.lastname: Lignon
authors.forename: M C
authors.initials: MC
authors.lastname: Galas
authors.forename: J
authors.initials: J
authors.lastname: Laur
authors.forename: P
authors.initials: P
authors.lastname: Worms
authors.forename: J
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism*; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D012844:Sincalide; D004298:Dopamine