D1 dopamine receptors in human putamen, frontal cortex and calf retina: differences in guanine nucleotide regulation of agonist binding and adenylate cyclase stimulation.

High-affinity binding sites for the D1 dopamine receptor antagonist [3H]SCH 23390 were identified in membranes from human putamen, frontal cortex and calf retina. In frontal cortex binding not only occurred to D1 but also to 5-HT2 receptors. In retina and putamen no binding to 5-HT2 receptors was detected. All further binding experiments in frontal cortex were carried out in the presence of 20 nM mianserin to prevent binding to 5-HT2 receptors. In the 3 tissues, antagonist competition curves were monophasic, whereas competition curves with the agonist dopamine revealed the presence of two binding sites, one having high affinity (RH) (32% in retina, 28% in putamen, and 15% in frontal cortex) and the other having low affinity (RL). In retina, the addition of 100 microM GTP caused a full conversion of RH into RL. In contrast, in frontal cortex, RH sites were not altered by 400 microM GTP or 100 microM 5'-guanylyl-imidodi-phosphate (Gpp(NH)p). In putamen, both guanine nucleotides provoked only a partial conversion of RH into RL. Dopamine (100 microM) produced a 220% and 56% increase in cAMP production in respectively retina and putamen homogenates, while no increase was observed in frontal cortex homogenate. These data may suggest that not all D1-receptors are coupled to the adenylate cyclase system.