Interactions between adenosine A2a and dopamine D2 receptors in the control of [3H]GABA release in the globus pallidus of the rat

The interactions between adenosine A2A receptors and dopamine D2 receptors on the modulation of depolarization-evoked [3H]-γ-amino-butyric-acid release (GABA) were examined in slices of the globus pallidus of the rat. The stimulation of release caused by activation of A2A receptors was blocked when dopaminergic influences were eliminated with three independent methods: a) antagonism of D2 receptors with sulpiride; b) alkylation of these receptors with N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ); c) depletion of dopamine with reserpine. In turn, activation of A2A receptors modified the response to stimulation of D2 receptors: the EC50 for quinpirole increased nearly one thousand times when A2A receptors were stimulated. Antagonism of A2A receptors in the absence of added agonists inhibited [3H] GABA release indicating receptor occupancy by endogenous adenosine. The dopamine dependence and the large effects of activating A2A receptors on the potency of dopaminergic agonists clarify some of the therapeutic properties of A2A antagonists in parkinsonian animals and patients.