The A3 adenosine receptor: history and perspectives.
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): A(1), A(2)A, A(2)B, and A(3). The A(3) adenosine receptor (A(3)AR) 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, A(3)AR 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 A(3) agonists or antagonists would be the best choice. Today, the choice has been made and A(3)AR 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 A(3)AR 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.
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.).
Pier Andrea
PA
Borea
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.) vrk@unife.it mhs@unife.it.
Katia
K
Varani
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.).
Fabrizio
F
Vincenzi
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.).
Pier Giovanni
PG
Baraldi
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.).
Mojgan Aghazadeh
MA
Tabrizi
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.) vrk@unife.it mhs@unife.it.
Stefania
S
Merighi
Department of Medical Sciences, Pharmacology Section (P.A.B., K.V., F.V., S.M., S.G.), and Department of Pharmaceutical Sciences, University of Ferrara, Italy (P.G.B., M.A.T.).
Stefania
S
Gessi
D000241:Adenosine / Q000378:metabolism*; D058909:Adenosine A3 Receptor Agonists / Q000627:therapeutic use; D058918:Adenosine A3 Receptor Antagonists / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015195:Drug Design; D049673:History, 20th Century; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D043684:Receptor, Adenosine A3 / Q000187:drug effects / Q000266:history / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D008024:Ligands; D043684:Receptor, Adenosine A3; D000241:Adenosine