D1 and D2 Dopamine Receptors in Caudate‐Putamen of Nonhuman Primates (Macaca fascicularis)

Abstract

D₁ and D₂ dopamine receptors were characterized in the caudate-putamen region of nonhuman primate brains (Macaca fascicularis). D₁ dopamine receptors were identified with [³H]SCH 23390 and D₂ receptors with [³H]-spiperone. Scatchard analysis of [³H]SCH 23390 saturation data using washed membranes revealed a single high-affinity binding site (K_D, 0.352 ± 0.027 nM) with a density (Bmax) of 35.7 ± 2.68 pmol/g original wet tissue weight (n = 10). The affinity of [³H]spiperone for the D₂ site was 0.039 ± 0.007 nMand the density was 25.7 ± 1.97 pmol/g original wet tissue weight (n = 10). D₁ and D₂ receptors in nonhuman primates may be differentiated on the basis of drug affinities and stereoselectivity. In competition experiments, RS-SKF 38393 was the most selective D₁ agonist, whereas (+)-4-propyl-9-hydroxynaphthoxazine [(+)-PHNO] was the most selective D₂ agonist. Apomorphine was essentially nonselective for D₁ or D₂ binding sites. Of the antagonists, R-SKF 83566 and SCH 23390 were the most selective for the D₁ site, whereas YM-09151–2 was the most selective for the D₂ site. cis-Flupentixol and (S)-butaclamol were the least selective dopamine antagonists. D₁ receptors bound benzazepine antagonists (SCH 23390/ SCH 23388, R-SKF 83692/RS-SKF 83692) stereoselectively whereas D₂ receptors did not. Conversely D₂ receptors bound (S)-sulpiride and (+)-PHNO more potently than their enantiomers whereas D₁ receptors showed little stereoselectively for each of these isomeric pairs. These binding characteristics may be utilized for evaluation of individual receptor function in vivo.