INTERACTIONS OF DOPAMINE AGONISTS WITH BRAIN D1 RECEPTORS LABELED BY H-3 ANTAGONISTS - EVIDENCE FOR THE PRESENCE OF HIGH AND LOW AFFINITY AGONIST-BINDING STATES

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 27  (2) , 171-183
Abstract
The interactions of dopaminergic agonists and antagonists with 3H-antagonist labeled D1 dopamine receptors of rat striatum were characterized. [3H]Flupentixol was found to selectively label D1 dopamine receptors when its binding to D2 dopamine receptors was blocked by the inclusion of D2 selective concentrations of unlabeled spiroperidol or domperidone. Antagonist/3H-antagonist competition curves are of uniformly steep slope (nH = 1.0) suggesting the presence of a single D1 dopamine receptor. Agonist/3H-antagonist competition curves are extremely shallow (nH .ltoreq. 0.5) for agonists of high relative efficacy, suggesting the presence of heterogeneous populations of agonist-binding states of the D1 dopamine receptor. Computer-modeling techniques were used to estimate affinities and relative site densities for these heterogeneous binding states. This analysis indicates that the ratio of agonist affinities for low and high affinity agonist-binding states is correlated with agonist relative efficacies in activating adenylate cyclase in membrane homogenates. Under the assay conditions employed, the addition of saturating concentrations of guanine nucleotides reduced, but did not abolish, the relative density of high affinity agonist-binding sites. These binding data can, at least in part, be explained by postulating 2 states of the D1 dopamine receptor, inducible by agonists but not by antagonists and modulated by guanine nucleotides.