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J. Biol. Chem., Vol. 263, Issue 22, 10641-10645, 08, 1988

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

C Mendre, M Rodriquez, C Gueudet, MF Lignon, MC Galas, J Laur, P Worms and J Martinez
Centre de Pharmacologie-Endocrinologie, Montpellier, France.

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.
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