Adenosine receptor A2A subtype (ADORA2A)

Adenosine receptor A2A subtype Overview

The Adenosine receptor A2A subtype is a member of the G protein-coupled receptor family that binds extracellular adenosine. It is encoded by the ADORA2A gene and features seven transmembrane domains typical of GPCRs. The A2A subtype couples primarily to stimulatory G proteins (Gs), leading to increased intracellular cAMP upon activation. It plays key roles in regulating neurotransmitter release—especially dopamine—in the central nervous system, modulating immune cell activity as an immune checkpoint molecule, controlling vascular tone through vasodilation, and influencing processes like angiogenesis and sleep-wake cycles.\n\nTherapeutically, it is targeted by both agonists and antagonists for indications ranging from cardiac stress testing to neurodegenerative diseases such as Parkinson's disease. Its role as an immune checkpoint has also made it a focus for cancer immunotherapy research. Structurally well-characterized through X-ray crystallography and cryo-electron microscopy studies,[6] it serves as a model system among GPCRs for drug discovery efforts.[1][3][4]

Mechanism of Action

Drugs targeting this molecule act primarily by either antagonizing or agonizing the adenosine binding site to modulate downstream G protein signaling. Antagonists block adenosine-mediated inhibition of dopamine D2 signaling in the striatum—relevant for Parkinson’s therapy. Agonists activate Gs proteins to increase cAMP levels and mediate vasodilation or immunosuppression.[1][3][4]

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers