Cholecystokinin-dopamine receptor interactions as studied with cholecystokinin receptor antagonists

It has previously been shown that cholecystokinin octapeptide (CCK-8) can modulate the binding of dopaminergic agonists and antagonists to brain homogenates in vitro. The present study was designed to more carefully address the possibility that CCK-8 could modulate the number of affinity of rat striatal D2 receptors. It was found that (1) unsulfated CCK-8 will antagonize the binding of tritiated spiperone to D2 receptors, but sulfated CCK-8 is considerably less potent; (2) the putative CCK antagonists benzotript, proglumide, and the phenoxyacetyl derivative of proglumide were without effect upon tritiated spiperone binding to D2 receptors up to concentrations of 100 microM; (3) the phenoxyacetyl derivative of proglumide, a potent CCK antagonist in the periphery, is only modestly more potent than proglumide in CCK receptor binding assays using 125-I-(Bolton-Hunter)-CCK-8. It is suggested that the modulatory actions of CCK upon D2 receptors do not appear to proceed through a recognition site corresponding to the conventional pharmacological definition of a neuronal CCK receptor.