A2AR

Adenosine A2A receptor (A2AR) is a G protein-coupled receptor that mediates the actions of the purine nucleoside adenosine. In humans it is encoded by the ADORA2A gene. A2AR belongs to the A2A adenosine receptor subtype, one of four adenosine receptor families (A1, A2A, A2B, A3).

Expression is highest in the striatum of the brain, particularly in neurons of the indirect pathway of the basal ganglia, where it co-localizes with D2 dopamine receptors. It is also found in other tissues, including the heart, vasculature, and immune cells, reflecting a broad role in physiology.

A2AR couples to heterotrimeric Gs proteins, stimulating adenylate cyclase and increasing intracellular cAMP, which activates protein kinase A and downstream signaling. It can form functional heteromers with D2 dopamine receptors, contributing to the regulation of motor control. Activation by adenosine typically dampens neurotransmitter release and modulates neuronal excitability.

Physiological and clinical relevance includes modulation of motor function and cardiovascular and immune processes. Antagonists of A2AR are used as adjuvant therapy in Parkinson's disease to reduce wearing-off symptoms associated with L-DOPA therapy (for example, istradefylline). Caffeine and other xanthines act as nonselective adenosine receptor antagonists. In peripheral tissues, A2AR activation promotes vasodilation and suppresses immune cell activity, which has drawn interest in inflammatory and transplant settings; conversely, A2AR antagonists are being explored to enhance cancer immunotherapy by relieving T cell suppression.