D-2 dopamine receptor-G protein coupling. Cross-regulation of agonist and guanosine nucleotide binding sites

The cross regulation of agonist binding to D-2 dopamine receptors and guano sine nucleotide binding to G proteins was studied using membranes of Chines e hamster ovary cells expressing rat D-2short dopamine receptors. All guano sine nucleotides studied caused a concentration-dependent loss of high-affi nity agonist binding sites of D-2 receptors with potencies corresponding to their affinity to bind to G proteins in these membranes. On the other hand , the dopaminergic agonists, but not antagonists, decreased the affinities of guanosine diphosphate and guanosine monophosphate, but not of guanosine 5'-(gamma -thiotriphosphate). The cross regulation of ligand binding to D-2 dopamine receptors and G proteins suggests the existence of several confor mational states of these proteins during the signal transduction and that t he high-affinity state of agonist binding is a transient state of the agoni st-receptor-G protein complex, where no nucleotides are bound. (C) 2001 Els evier Science Ireland Ltd. All rights reserved.