DOPAMINE D-1 RECEPTORS ARE INVOLVED IN THE MODULATION OF D-2 RECEPTORS INDUCED BY CHOLECYSTOKININ RECEPTOR SUBTYPES IN RAT NEOSTRIATAL MEMBRANES

The action of cholecystokinin octapeptide (CCK-8) on rat neostriatal d opamine (DA) D-2 receptors was evaluated in membrane binding experimen ts. 0.1 nM of CCK-8 increased the K-d value of the D-2 agonist [H-3]N- propylnorapomorphine (NPA) binding sites by 42%. The CCKB antagonist P D134308 blocked this action. Kinetic analysis demonstrated that this e ffect of CCK-8 was related to a reduction by 45% of the association ra te constant of [H-3]NPA. In contrast, 1 nM of CCK-8 decreased the K-H and the K-L values of DA for the D-2 antagonist [H-3]raclopride bindin g sites by 56% and 50%, respectively. Both the CCKA antagonist L364718 and the CCKB antagonist PD134303 blocked this effect. The D-1 antagon ist SCH23390 counteracted the CCK-8 induced decrease in the K-H and th e K-L values of DA, and allowed 1 nM of CCK-8 to produce a significant increase in the IC50 value of NPA for the [H-3]raclopride binding sit es. These results indicate that CCK-8 can reduce the affinity of the n eostriatal D-2 agonist binding sites, but increase the affinity of D-2 receptors for DA. D-1 receptors may exert a switching role in the mod ulation of the neostriatal D-2 receptors by the CCK receptors.