TY - JOUR T1 - The A<sub>3</sub> Adenosine Receptor: History and Perspectives JF - Pharmacological Reviews JO - Pharmacol Rev SP - 74 LP - 102 DO - 10.1124/pr.113.008540 VL - 67 IS - 1 AU - Pier Andrea Borea AU - Katia Varani AU - Fabrizio Vincenzi AU - Pier Giovanni Baraldi AU - Mojgan Aghazadeh Tabrizi AU - Stefania Merighi AU - Stefania Gessi A2 - Sibley, David R. Y1 - 2015/01/01 UR - http://pharmrev.aspetjournals.org/content/67/1/74.abstract N2 - By general consensus, the omnipresent purine nucleoside adenosine is considered a major regulator of local tissue function, especially when energy supply fails to meet cellular energy demand. Adenosine mediation involves activation of a family of four G protein–coupled adenosine receptors (ARs): A1, A2A, A2B, and A3. The A3 adenosine receptor (A3AR) is the only adenosine subtype to be overexpressed in inflammatory and cancer cells, thus making it a potential target for therapy. Originally isolated as an orphan receptor, A3AR presented a twofold nature under different pathophysiologic conditions: it appeared to be protective/harmful under ischemic conditions, pro/anti-inflammatory, and pro/antitumoral depending on the systems investigated. Until recently, the greatest and most intriguing challenge has been to understand whether, and in which cases, selective A3 agonists or antagonists would be the best choice. Today, the choice has been made and A3AR agonists are now under clinical development for some disorders including rheumatoid arthritis, psoriasis, glaucoma, and hepatocellular carcinoma. More specifically, the interest and relevance of these new agents derives from clinical data demonstrating that A3AR agonists are both effective and safe. Thus, it will become apparent in the present review that purine scientists do seem to be getting closer to their goal: the incorporation of adenosine ligands into drugs with the ability to save lives and improve human health. ER -