Adenosine receptor A1 and Adenosine receptor A2A (A1R and A2AR)

Adenosine receptor A1 and Adenosine receptor A2A are G protein-coupled receptors (GPCRs) that mediate the effects of the endogenous nucleoside adenosine in many tissues, including the heart, brain, and immune system. A1R is primarily coupled to the Gi protein and inhibits adenylate cyclase activity, with major roles in cardiac and neuronal signaling. A2AR mainly couples to Gs proteins to stimulate adenylate cyclase, exerting anti-inflammatory effects and modulating neurotransmission. They are established therapeutic targets for cardiovascular, neurodegenerative, and immune conditions, with several clinically relevant drugs—both agonists and antagonists—targeting these receptors. Selectivity and subtype-specific modulation present major challenges and opportunities for new therapies.

Other names

Adenosine receptor type A1 (A1R)Adenosine receptor type A2A (A2AR)A1 adenosine receptorA2A adenosine receptorP1 receptor subtypes (family)

Agonists (e.g., adenosine, NECA) activate the receptor, leading to intracellular signaling via G protein pathways, modulating adenylate cyclase and downstream signaling. Antagonists (e.g., caffeine, theophylline, Istradefylline, Etrumadenant) block the receptor, inhibiting adenosine-mediated signaling, affecting neurotransmitter release, inflammation, and cardiovascular functions.