Adenosine A_2A receptor (A_2AR)

Adenosine A_2A receptor is a G-protein-coupled adenosine receptor that mediates immunomodulatory, striatal, and tumor-microenvironment signaling responses^[1][2][3]. Mechanistically, inosine activates A_2AR and drives cAMP production and ERK1/2 phosphorylation, showing ERK1/2-biased signaling compared with adenosine^[1]. In inflammatory cells, A2 receptor activation inhibits lipopolysaccharide-stimulated TNF-α production, and the A2 agonist CPCA is far more effective than the A1 agonist CCPA^[4]. In Parkinson’s disease models, A_2A antagonists target GABAergic striatopallidal medium spiny neurons and improve motor deficits without worsening dyskinesia^[2][5][6]. In tumors, extracellular adenosine suppresses antitumor immunity through A_2AR on infiltrating immune cells, supporting A_2AR blockade as an immuno-oncology strategy^[3][7]. Compared with related isoforms, A_2AR is distinguished experimentally by selective antagonists such as CGS 15943 and KW6002, whereas DMX-7R is described as a partial A1 agonist^[2][8]. For research applications, A_2AR agonists and antagonists enable pathway testing across cAMP, ERK1/2, GABAergic transmission, and tumor immune suppression models^[1][2][3][7].