Dopaminergic D-3 binding sites are not presynaptic autoreceptors.
Postsynaptic dopamine (DA) receptors have been classified biochemically and pharmacologically into two types: D-1 receptors mediate adenylate cyclase stimulation, demonstrating micromolar affinity for DA and butyrophenone antagonists; D-2 receptors mediate adenylate cyclase inhibition, demonstrating nanomolar affinity for DA and butyrophenone antagonists. D-1 receptors are labelled by 3H-thioxanthene antagonists, while D-2 receptors are labelled by both 3H-agonists and all 3H-antagonists. A third class of dopaminergic binding site, termed D-3, represents high-affinity 3H-agonist binding sites demonstrating low, micromolar, affinity for butyrophenones. In the rat striatum, D-3 sites were decreased 50% by 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal DA pathway, suggesting that such D-3 binding labels presynaptic DA autoreceptors on nigrostriatal terminals. However, nigrostriatal denervation produces a concomitant depletion of striatal DA. Here we demonstrate that a reserpine-induced depletion of DA produces a decrease in D-3 binding comparable to that seen with nigrostriatal denervation, independent of presynaptic terminal degeneration. This loss in binding, or that caused by 6-OHDA lesions, is recovered by preincubating the striatal membranes with DA or with the supernatant from control striatal membrane preparations. We therefore suggest that the loss of D-3 binding following 6-OHDA lesions results from the depletion of endogenous DA rather than the degeneration of terminals and their putatively associated autoreceptors.
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D003714:Denervation; D006892:Hydroxydopamines / Q000494:pharmacology; D009434:Neural Pathways / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013378:Substantia Nigra / Q000378:metabolism
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D013134:Spiperone; D012110:Reserpine; D016627:Oxidopamine