Adenosine receptor A3 (ADORA3) (ADORA3)

The Adenosine receptor A3 (ADORA3) is a G protein-coupled receptor (GPCR) that plays a critical role in modulating inflammatory responses, cell survival, and immune signaling [1, 4]. It is primarily coupled to the Gi protein, which inhibits adenylyl cyclase and reduces intracellular cyclic AMP (cAMP) levels, although it can also signal through Gq proteins to activate phospholipase C [4, 17]. ADORA3 is notably overexpressed in inflammatory and cancer cells compared to normal tissues, making it a highly specific therapeutic target [6, 10]. Activation of the receptor by selective agonists, such as piclidenoson and namodenoson, has been shown to deregulate the NF-kappaB and Wnt/beta-catenin signaling pathways, leading to the apoptosis of pathological cells in conditions like psoriasis, rheumatoid arthritis, and hepatocellular carcinoma [6, 11]. Beyond its role in inflammation and oncology, ADORA3 is involved in cardioprotection during ischemic events and is being explored for the treatment of glaucoma and neuropathic pain [4, 7, 13].

Other names

A3ARADORA3A3 receptorAD026

Agonism of the Gi-coupled receptor leads to inhibition of adenylyl cyclase, reduction of cAMP, and deregulation of NF-kappaB and Wnt/beta-catenin signaling pathways, ultimately inducing apoptosis in pathological cells [4, 6, 10].