Adenosine receptor A1, A2A, and A2B (ADORA1, ADORA2A, ADORA2B)

The A1, A2A, and A2B adenosine receptors are a group of G-protein-coupled receptors (GPCRs) that mediate the physiological effects of the endogenous nucleoside adenosine across various tissues [1, 5]. These receptors are members of the P1 purinergic receptor family and are distinguished by their primary G-protein coupling: the A1 receptor typically couples to Gi/o proteins to inhibit adenylyl cyclase, while the A2A and A2B receptors couple to Gs proteins to stimulate it [7, 10]. They play vital roles in the central nervous system, where they modulate neurotransmitter release and neuroinflammation, and in the cardiovascular system, where they regulate heart rate and vascular tone [4, 6, 11]. Due to their involvement in conditions such as Parkinson's disease, cardiac arrhythmias, asthma, and cancer, they are significant therapeutic targets [1, 3, 13]. Drugs interacting with these receptors range from non-selective antagonists like caffeine and theophylline to highly selective agents like the A2A agonist regadenoson and the A2A antagonist istradefylline [5, 9].

Other names

P1 receptorsAdenosine A1 receptorAdenosine A2A receptorAdenosine A2B receptorADORA1ADORA2AADORA2B

Drugs targeting these receptors act as either agonists or antagonists to modulate intracellular signaling. A1 agonists activate Gi/o proteins to inhibit adenylyl cyclase, decreasing cAMP levels and reducing neurotransmitter release or heart rate [7, 9]. A2A and A2B agonists activate Gs proteins to stimulate adenylyl cyclase, increasing cAMP levels to promote vasodilation or suppress immune activity [7, 13]. Antagonists, such as caffeine, competitively block endogenous adenosine from binding, thereby preventing these inhibitory or stimulatory cascades [5, 10].