Opposing actions of an adenosine A2 receptor agonist and a GTP analogue on the regulation of dopamine D2 receptors in rat neostriatal membranes.

We have previously found, in rat striatal membrane preparations, that stimulation of adenosine A2 receptors (with the selective adenosine A2 receptor agonist CGS 21680) increases the high- and low-affinity dissociation constants and increases the proportion of high-affinity dopamine D2 receptor binding sites labelled with the selective dopamine D2 receptor antagonist [3H]raclopride. As guanine nucleotides and divalent cations (such as Mg2+) are known to regulate the proportion of high-affinity D2 receptor binding sites in opposing ways, interaction experiments with CGS 21680, the GTP analogue Gpp(NH)p and MgCl2 were performed. Our results suggest that these three factors exert significant, though independent, effects on the proportion of high affinity D2 receptors, and that A2 receptors regulate both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G-protein.