Adenosine A2 receptor (ADORA2)

Adenosine A2 receptors are a class of G protein-coupled receptors (GPCRs) comprising the A2A and A2B subtypes, which play pivotal roles in cardiovascular, neurological, and immunological signaling. These receptors are primarily activated by extracellular adenosine, leading to the stimulation of adenylyl cyclase and subsequent increases in intracellular cyclic AMP (cAMP) [UniProt, 2024]. The A2A receptor is highly expressed in the brain's striatum and on various immune cells, where it acts as a critical regulator of motor coordination and an "off-switch" for the immune response [PubMed, 2022]. In contrast, the A2B receptor has a lower affinity for adenosine and is typically upregulated during conditions of hypoxia or inflammation, contributing to vascular remodeling and cytokine regulation [PubChem, 2024]. Therapeutically, A2A antagonists like istradefylline are used to manage motor fluctuations in Parkinson's disease, while A2A agonists such as regadenoson are employed in cardiac stress testing to induce vasodilation [FDA, 2019]. Furthermore, the A2 receptor family is a major focus in immuno-oncology, where blocking adenosine signaling is explored as a strategy to enhance the anti-tumor activity of T-cells [Journal for ImmunoTherapy of Cancer, 2021].

Other names

A2 receptorAdenosine receptor A2ADORA2A2A receptorA2B receptor

Adenosine A2 receptors primarily act through Gs protein-mediated activation of adenylyl cyclase, increasing intracellular cAMP levels [UniProt, 2024]. Specific mechanisms include: 1) A2A receptor antagonism to reduce GABAergic inhibition in the striatum for Parkinson's disease [PubMed, 2021]; 2) A2A receptor agonism to induce coronary vasodilation for diagnostic imaging [StatPearls, 2023]; 3) A2A receptor antagonism to block adenosine-mediated T-cell suppression in the tumor microenvironment [Nature Reviews Drug Discovery, 2020]; and 4) A2B receptor modulation to regulate inflammatory cytokine release [Journal of Clinical Investigation, 2018].