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D 1 and D 2 Dopamine Receptors in Caudate‐Putamen of Nonhuman Primates ( Macaca fascicularis )
Author(s) -
Madras Bertha K.,
Fahey Michele A.,
Canfield Don R.,
Spealman Roger D.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb01830.x
Subject(s) - spiperone , sch 23390 , apomorphine , agonist , dopamine receptor , receptor , sulpiride , chemistry , dopamine agonist , dopamine , endocrinology , medicine , biology , antagonist , biochemistry
D 1 and D 2 dopamine receptors were characterized in the caudate‐putamen region of nonhuman primate brains ( Macaca fascicularis ). D 1 dopamine receptors were identified with [ 3 H]SCH 23390 and D 2 receptors with [ 3 H]‐spiperone. Scatchard analysis of [ 3 H]SCH 23390 saturation data using washed membranes revealed a single high‐affinity binding site ( K D , 0.352 ± 0.027 n M ) with a density ( B max) of 35.7 ± 2.68 pmol/g original wet tissue weight (n = 10). The affinity of [ 3 H]spiperone for the D 2 site was 0.039 ± 0.007 n M and the density was 25.7 ± 1.97 pmol/g original wet tissue weight (n = 10). D 1 and D 2 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 D 1 agonist, whereas (+)‐4‐propyl‐9‐hydroxynaphthoxazine [(+)‐PHNO] was the most selective D 2 agonist. Apomorphine was essentially nonselective for D 1 or D 2 binding sites. Of the antagonists, R ‐SKF 83566 and SCH 23390 were the most selective for the D 1 site, whereas YM‐09151–2 was the most selective for the D 2 site. cis ‐Flupentixol and ( S )‐butaclamol were the least selective dopamine antagonists. D 1 receptors bound benzazepine antagonists (SCH 23390/ SCH 23388, R ‐SKF 83692/ RS ‐SKF 83692) stereoselectively whereas D 2 receptors did not. Conversely D 2 receptors bound (S)‐sulpiride and (+)‐PHNO more potently than their enantiomers whereas D 1 receptors showed little stereoselectively for each of these isomeric pairs. These binding characteristics may be utilized for evaluation of individual receptor function in vivo.