Adenosine A2A receptor (A2AR) (A2AR)

The Adenosine A2A receptor (A2AR) is a high-affinity G protein-coupled receptor (GPCR) that plays a critical role in regulating various physiological processes, including neurotransmission, cardiovascular function, and immune responses [1, 6, 8]. It is primarily coupled to the Gs protein, and its activation by the endogenous ligand adenosine leads to an increase in intracellular cyclic AMP (cAMP) levels [1, 5, 11]. In the central nervous system, A2AR is highly expressed in the striatum, where it modulates dopaminergic activity and is a key target for treating Parkinson's disease [2, 8, 13]. In the periphery, it is found on immune cells and blood vessels, where it mediates anti-inflammatory effects and vasodilation [3, 15, 17]. Pharmacologically, A2AR is targeted by agonists for cardiac stress testing and by antagonists for neurodegenerative diseases and immuno-oncology, where blocking the receptor can enhance anti-tumor immune responses [5, 6, 10, 19].

Other names

ADORA2AAdenosine receptor A2aRDC8A2aRAdenosine A2 receptor

Adenosine A2A receptor ligands function as either agonists or antagonists to modulate intracellular signaling. Agonists, such as regadenoson, bind to the receptor and activate Gs proteins, which stimulate adenylyl cyclase to increase intracellular cyclic AMP (cAMP) levels, leading to smooth muscle relaxation and vasodilation [1, 5, 11]. Antagonists, such as istradefylline, block the receptor to prevent adenosine-mediated signaling; in the brain, this modulates the indirect pathway of the basal ganglia to improve motor function in Parkinson's disease, while in the tumor microenvironment, it prevents the suppression of T-cell activity, thereby enhancing anti-tumor immunity [2, 5, 8, 13].