Adenosine receptors A1, A2B, and A3 (A1R, A2BR, A3R)

Adenosine receptors A1, A2B, and A3 are members of the purinergic P1 GPCR family, widely expressed in human tissues where they mediate the physiological effects of adenosine. Each subtype couples to distinct G proteins, producing different biochemical effects: A1 and A3 generally inhibit adenylyl cyclase (via Gi proteins) to decrease cAMP, while A2BR primarily stimulates cAMP production (via Gs proteins)[4][2][3][1]. The A1 receptor is mainly found in the central nervous system and heart, where it promotes neuroprotection and reduces heart rate. The A2B receptor is prominent in peripheral tissues such as the lung and vasculature, modulating inflammation and vascular tone. The A3 receptor is expressed in immune tissues and cancer cells, and is involved in immune modulation and cell death pathways[2][3][1][4]. Therapeutic modulation of these receptors is being pursued in a variety of diseases, but achieving clinical success depends on developing ligands with high receptor subtype selectivity and minimizing off-target/safety issues[3][2][4][1].

Other names

Adenosine A1 receptorA1 adenosine receptorAdenosine A2B receptorA2B adenosine receptorAdenosine A3 receptorA3 adenosine receptorP1 receptors

Agonists stimulate the receptor, modulating intracellular cAMP and downstream kinase signaling pathways (e.g., ERK, JNK, p38), protein kinase C, and calcium flux; the precise effect is subtype-dependent. Antagonists block the receptor, preventing endogenous adenosine from exerting its effects—commonly resulting in stimulant or anti-inflammatory outcomes (caffeine and theophylline block A1R and A2A).