Adenosine A2B and A3 receptors (ADORA2B/ADORA3)

The Adenosine A2B and A3 receptors are G protein-coupled receptors (GPCRs) that serve as critical sensors of extracellular adenosine, which accumulates during metabolic stress, hypoxia, and tissue injury [2, 5, 16]. The A2B receptor is a low-affinity subtype that is typically upregulated in inflammatory environments, where it couples to Gs and Gq proteins to promote processes such as angiogenesis, cell proliferation, and the release of pro-inflammatory cytokines [4, 10, 22]. In contrast, the A3 receptor is a high-affinity subtype coupled to Gi and Gq proteins, involved in modulating immune responses, providing cardioprotection during ischemia, and regulating cell survival [1, 3, 5]. In respiratory conditions like asthma and COPD, both receptors contribute to mast cell degranulation and airway hyperresponsiveness, making dual A2B/A3 antagonists like QAF805 a focus of therapeutic research [9, 21, 24]. Additionally, selective A3 agonists such as piclidenoson and namodenoson are being evaluated in clinical trials for their ability to induce apoptosis in cancer cells and suppress inflammation in autoimmune diseases like rheumatoid arthritis and psoriasis [17, 19]. The development of drugs targeting these receptors is challenged by significant species-specific differences in pharmacology and the dualistic roles these receptors can play in acute versus chronic disease states [16, 23, 26]. A2B receptor activation is also linked to metabolic regulation in diabetes and renal protection, while A3 receptor signaling is explored for neuroprotection and glaucoma treatment [1, 4, 16]. Overall, these receptors represent versatile therapeutic targets across oncology, immunology, and cardiovascular medicine [16, 26].

Other names

A2BARA3ARAdenosine receptor A2BAdenosine receptor A3ADORA2BADORA3

Antagonism of A2B and A3 receptors to inhibit mast cell degranulation and airway inflammation; Agonism of A3 receptors for anti-inflammatory, cardioprotective, and anti-tumor effects.