DOPAMINE-INDUCED REDUCTION IN THE DENSITY OF GUANINE NUCLEOTIDE-SENSITIVE D-1 RECEPTORS IN HUMAN POSTMORTEM BRAIN IN THE ABSENCE OF APPARENT D-1-D-2 INTERACTIONS

The effects of dopamine and guanine nucleotides on the binding of the D-1 dopamine receptor antagonist ligand [H-3]SCH 23390 were examined i n membranes prepared from putamen, caudate and nucleus accumbens of hu man postmortem brain. Dopamine induced a concentration-dependent decre ase in the apparent maximum number of binding sites (B-max) in each br ain region studied, and displaced binding in a biphasic manner consist ent with the presence of both high and low affinity states of the D, r eceptor; the GTP analogue Gpp(NH)p transformed this biphasic displacem ent to a monophasic pattern consistent with a shift of high affinity s ites to a low affinity state. However, the selective D-2 antagonist et iclopride did not reverse the action of dopamine to decrease B-max. Th ese data suggest that dopamine decreases B-max for D-1 receptors throu gh a high affinity, guanine nucleotide-sensitive agonist binding site, but fail to reveal D-1:D-2 interactions at this synaptic level.