Multiple intramembrane receptor-receptor interactions in the regulation ofstriatal dopamine D-2 receptors

ADENOSINE A(2A), group I mGlu and neurotensin receptors have been previousl y found to modulate the binding characteristics of dopamine D-2 receptors i n membrane preparations from rat striatum. In the present study it is shown that stimulation of different combinations of striatal A(2A), group I mGlu and neurotensin receptors induce different effects on the modulation of D- 2 receptor binding to those obtained when they are separately stimulated us ing maximal effective concentrations. In competitive inhibition experiments of dopamine versus the D-2 receptor antagonist [H-3]raclopride the additio n of the A(2A) receptor agonist CGS 21680, the group I mGlu receptor agonis t DHPG or neurotensin induced a decrease in the affinity of the high affini ty state of the dopamine D-2 receptors for dopamine. When added together CG S 21680 plus neurotensin induced the same effect as when administered alone , CGS 21680 plus DHPG induced a synergistic effect and DHPG plus neurotensi n lost their modulating effect on D-2 receptor binding. these results demon strate the existence of multiple intramembrane receptor-receptor interactio ns in the regulation of striatal D-2 receptors. NeuroReport 10:2051-2054 (C ) 1999 Lippincott Williams & Wilkins.