Adenosine receptor type 2B (A2B)

Adenosine receptor type 2B (ADORA2B) is a G protein-coupled receptor (GPCR) that plays a vital role in tissue adaptation to stressful conditions, such as hypoxia, ischemia, and inflammation [UniProt, PubMed]. Characterized by its relatively low affinity for its endogenous ligand, adenosine, the A2B receptor is primarily activated when adenosine concentrations reach high levels in pathological microenvironments [PubMed, NCBI]. Upon activation, the receptor typically signals through Gs proteins to stimulate adenylate cyclase and increase intracellular cAMP, although it can also signal through Gq pathways to trigger calcium mobilization in certain cell types [Wikipedia, PubMed]. This receptor is a key regulator of diverse biological processes, including vascular integrity, angiogenesis, and the production of inflammatory cytokines such as IL-6 and IL-10 [PubMed, NCBI]. In disease contexts, the A2B receptor is frequently upregulated in various solid tumors, where it facilitates an immunosuppressive tumor microenvironment, promotes cancer cell proliferation, and supports metastasis [PubMed, ASCO]. As a result, selective A2B antagonists are being developed as novel cancer immunotherapies, often aimed at reversing adenosine-mediated suppression of T cells and natural killer cells [PubMed, ASCO]. Additionally, the A2B receptor is investigated as a therapeutic target for asthma, due to its role in mast cell degranulation, and for metabolic diseases like diabetes and cardiovascular disorders, where its activation can exert protective effects [PubMed, NCBI]. Clinical development currently focuses on small-molecule modulators that can selectively target the A2B receptor while minimizing off-target interactions with other adenosine receptor subtypes [PubMed, ASCO].

Other names

ADORA2BAdenosine receptor A2bAA2BRAdenosine A2b receptorADORA2

Adenosine receptor antagonism, Adenosine receptor agonism, Competitive inhibition, and G protein-coupled receptor modulation [PubMed, NCBI]