Adenosine receptor A2a, Adenosine receptor A2b, and Adenosine receptor A3 (ADORA2A, ADORA2B, ADORA3)

The Adenosine receptor A2a, Adenosine receptor A2b, and Adenosine receptor A3 are members of the P1 purinergic G protein-coupled receptor (GPCR) family, which are activated by the endogenous nucleoside adenosine [1, 3]. These receptors play critical roles in modulating physiological processes such as neurotransmission, cardiovascular function, and immune responses [2, 5]. The A2A and A2B receptors are primarily coupled to Gs proteins, stimulating adenylyl cyclase and increasing intracellular cAMP, whereas the A3 receptor is coupled to Gi and Gq proteins [3, 10]. In disease, A2A receptors are key targets in Parkinson's disease and immuno-oncology, where their blockade can enhance anti-tumor immunity [2, 4]. A2B receptors are implicated in asthma and inflammation, particularly under hypoxic conditions, while A3 receptors are explored for their roles in autoimmune diseases and liver disorders [6, 12]. Pharmacological modulation includes both agonists, such as regadenoson for cardiac stress testing, and antagonists like istradefylline for neurodegeneration [1, 9].

Other names

Purinergic P1 receptorsA2AARA2BARA3ARADORA2AADORA2BADORA3Adenosine A2A receptorAdenosine A2B receptorAdenosine A3 receptor

Drugs targeting these receptors act as either agonists or antagonists to modulate intracellular signaling pathways, primarily through Gs-mediated increases in cAMP (A2A, A2B) or Gi/Gq-mediated decreases in cAMP and calcium mobilization (A3) [1, 3, 10].