Adenosine A3 receptor (ADORA3) (ADORA3)

The Adenosine A3 receptor (ADORA3) is a G protein-coupled receptor that plays a pivotal role in modulating inflammatory responses and cell survival (Jacobson & Gao, 2006). In guinea pigs, the A3 receptor is highly expressed in lung tissue, where its activation leads to mast cell degranulation and potent bronchoconstriction, making it a significant model for studying asthma and airway hyperresponsiveness (Kohno et al., 1996). This receptor signals primarily through the inhibition of adenylate cyclase and the activation of phospholipase C and D, influencing pathways such as NF-κB and Wnt (IUPHAR/BPS Guide to Pharmacology). In humans, ADORA3 is often overexpressed in inflammatory and cancer cells, which has led to the development of agonists like Piclidenoson for rheumatoid arthritis and Namodenoson for liver cancer (Fishman et al., 2012; Can-Fite BioPharma). Conversely, A3 receptor antagonists are being explored for their potential in treating respiratory diseases and glaucoma (Gessi et al., 2008). The pharmacological profile of the A3 receptor varies significantly across species, which is a critical consideration when translating findings from guinea pig models to human clinical applications (Linden, 2001).

Other names

A3ARA3 adenosine receptorAdenosine receptor A3ADORA3

Agonism of the A3 receptor leads to the inhibition of adenylyl cyclase and the activation of phospholipase C and D, which modulates downstream signaling pathways such as NF-κB and PI3K/Akt to exert anti-inflammatory and pro-apoptotic effects. Antagonism is primarily explored to block adenosine-induced bronchoconstriction and inflammatory cell recruitment in respiratory conditions.