Extracellular adenosine mediates a multitude of biological effects, including wakefulness, antiarrythmia, bronchoconstriction and response to ischemia and oxidative stress. A family of four G protein-coupled adenosine receptors, A1, A2A, A2B and A3, is responsible for these effects. A2A, which couples to Gs, is expressed in basal ganglia and immune cells. A2A reduces ischemia-induced inflammation; however, A2A antagonists protect from neurodegeneration during Parkinson"s disease. Caffeine, the most widely used psychoactive drug, is a nonselective adenosine receptor antagonist, but its psychomotor stimulant affect is attributed to A2A expressed on striatal projection neurons.