Comparative biochemical pharmacology of central nervous system dopamine D1 and D2 receptors.
The biochemical properties of central nervous system (CNS) dopamine (DA) D1 and D2 receptors were examined using the specific antagonists [3H]SCH23390 and [3H]raclopride, respectively. There is a different participation of sulfhydryl (-SH) and disulfide (-SS-) groups in the binding site and/or coupling to second messenger systems of D1 and D2 receptors. The ionic studies with [3H]SCH23390 showed slight agonist and antagonist affinity shifts for the D1 receptor. On the other hand, the D2 receptor is very sensitive to cations; even if lithium and sodium influence specific [3H]raclopride binding in a similar manner, there appear to be quantitative differences between these two ions that cannot be explained by surface charge mechanisms. The distribution of D1 and D2 receptors was heterogenous in both species, with the greatest densities in the neostriatum, where the highest concentrations of DA and metabolites were measured. Regions with low endogenous DA content (cerebral cortex and hippocampus) had lower densities of DA receptors. Furthermore, these binding sites were differentially localized within the various regions, and there were substantially more D1 than D2 receptors. The functional significance and heterogeneities in the distribution of D1 and D2 receptors can be related to dopaminergic innervation and turnover.
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Département de Physiologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Molina-Holgado
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Dewar
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D000375:Aging / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004220:Disulfides / Q000032:analysis; D065127:Dopamine D2 Receptor Antagonists; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D011817:Rabbits; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000032:analysis; D014316:Tritium
D001552:Benzazepines; D001679:Biogenic Amines; D004220:Disulfides; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D013438:Sulfhydryl Compounds; D014316:Tritium; D020891:Raclopride