Human Adenosine A2A Receptor (ADORA2A)

The Human Adenosine A2A Receptor is a member of the G protein-coupled receptor family that responds to extracellular adenosine. It features seven transmembrane helices and mediates cell signaling via Gs proteins, primarily increasing cAMP. The receptor is expressed throughout the brain (notably the striatum and nucleus accumbens), as well as in cardiovascular and immune cells. It forms functional heteromers with other receptors, including dopamine D2, which underpins several pharmacological effects. A2A antagonists are approved treatments for Parkinson’s disease, and modulators are in active development for cancer immunotherapy due to their role as immune checkpoints. Structural studies have revealed detailed binding pockets for orthosteric and allosteric ligands, enabling precise drug design.

Other names

Adenosine A2A receptorA2ARADORA2A

Antagonists block adenosine-mediated G-protein (Gs) activation, inhibiting downstream cyclic AMP (cAMP) signaling. Agonists activate the receptor, increasing cAMP via Gs coupling, leading to cell signaling changes affecting neurotransmission, vasodilation, and immune modulation. Allosteric modulators target secondary binding pockets with subtype selectivity.