Effect of Guanine Nucleotides on Dopaminergic Agonist and Antagonist Affinity for [3H]Sulpiride Binding Sites in Rat Striatal Membrane Preparations

Abstract

[3H]Sulpiride bound to rat striatal membrane preparations with a saturable, high affinity component. This binding was displaced potently by dopamine antagonists (both classic neuroleptics [fluphenazine, cis-flupenthixol] and the benzamide, sulpiride) and less potently by dopamine agonists [dopamine, apomorphine, ADTN [2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene] (a cyclic dopamine analog)]. GTP and its stable analog Gpp(NH)p [guanyl-5''-yl imidodiphosphate] did not affect [3H]sulpiride binding to the membranes but altered the affinity for dopaminergic agonists. This effect was specific in that antagonist binding was not affected and only GTP, GDP and Gpp(NH)p produced the effect. Similar alterations in ligand binding affinity caused by guanine nucleotides were observed for binding sites linked to an adenylate cyclase. Such an interpretation for the case of [3H]sulpiride is contrary to suggestions that sulpiride labels only those dopamine receptors that are not cyclase linked.