Adenosine A1 receptor, Adenosine A2A receptor, Adenosine A2B receptor (A1AR, A2AAR, A2BAR)

Adenosine A1, A2A, and A2B receptors are three of the four subtypes of adenosine receptors, which are G protein-coupled receptors (GPCRs) activated by the endogenous nucleoside adenosine. These receptors exhibit distinct tissue distributions and differ in their affinity for adenosine, coupling to various G proteins. The A1 receptor protects neurons and the heart, primarily mediating inhibitory effects in the CNS and cardioprotective actions; the A2A receptor modulates neuroinflammation and is implicated in Parkinson’s disease and cancer immunotherapy; the A2B receptor has lower affinity for adenosine and functions in inflammatory and metabolic regulation, linked to conditions such as asthma, diabetes, and vascular injury. All are therapeutic targets for a wide range of diseases, with selective agonists and antagonists in clinical and preclinical development. The main therapeutic challenge is achieving receptor subtype selectivity to minimize adverse effects.

Other names

Adenosine receptor A1, Adenosine receptor A2A, Adenosine receptor A2BADORA1 (gene symbol for A1AR), ADORA2A (A2AAR), ADORA2B (A2BAR)AR1, AR2A, AR2B (less common)

Antagonists block receptor activation reducing adenosine signaling (e.g., caffeine, istradefylline). Agonists stimulate receptor, modulating cell responses (e.g., regadenoson for vasodilation). Depending on the subtype: inhibition of neuronal activity, induction of vasodilation, suppression of inflammatory signaling, cardioprotection, etc.