Adenosine A2a Receptor Modulation of Electrically Evoked Endogenous GABA Release from Slices of Rat Globus Pallidus

Abstract

Adenosine A_2a receptors have been localized to GABAergic striatopallidal neurons, but their functional role is unknown. To address this question, the modulation of endogenous GABA release by adenosine A_2a receptors was examined in slices of rat globus pallidus. The selective adenosine A_2a receptor agonist CGS-21680 (3.0–10 nM) significantly increased electrically stimulated release (overflow) of GABA, with 10 nM CGS-21680 resulting in a 44% increase compared with the control. Both the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 μM) and the selective A_2a receptor antagonist KF-17837 (100 nM) abolished the CGS-21680-induced increase in GABA overflow. Higher concentrations of CGS-21680 (0.10–1.0 μM) decreased GABA overflow by ˜25%.8-Phenyltheophylline (10 μM) antagonized these effects, whereas KF-17837 (100 nM) did not, suggesting actions of CGS-21680 on other adenosine receptors at these concentrations. These results demonstrate that activation of adenosine A_2a receptors augments electrically stimulated release of GABA from globus pallidus slices and suggest a mechanism by which adenosine may modulate GABAergic output from the striatopallidal efferent system.