Antagonistic A_2a/D₂ receptor interactions in the striatum as a basis for adenosine/dopamine interactions in the central nervous system

Abstract

Abstract From behavioural and biochemical experiments, we have found evidence for the existence of a specific adenosine A 2a receptor/dopamine D 2 receptor interaction in the brain. Behavioural data show that stimulation A 2a receptors inhibits and their blockade potentiates a D 2 ‐mediated locomotor activation in mice and that stimulation of D 2 receptors counteracts on A 2a mediated cataleptic effect in rats. Biochemical data show that, in rat striatal membrane preparations, A 2a receptor stimulation decreases the affinity of D 2 receptors and the transduction of the signal from the D 2 receptor to the G‐protein. Based on these findings it is postulated that this A 2a /D 2 interaction might be the main mechanism responsible for the central effects of adenosine agonists and antagonists, like methylxanthines. The increased behavioural effect of methylxanthines after dopamine denervation could be explained by an increased interaction between adenosine A 2a and dopamine D 2 receptors. Membrane preparations‐denervated striatum are more sensitive to the effect of adenosine A 2a receptor stimulation. Our results underline the potential antiparkinsonian action of adenosine A 2a antagonists and the potential antipsychotic of adenosine A 2a agonists. © 1993 Wiley‐Liss, Inc.