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.
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology*; D014793:Visual Cortex / Q000378:metabolism*
D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D002766:Cholecystokinin; D012844:Sincalide; D004298:Dopamine