Adenosine is an endogenous nucleoside generated locally in tissues under conditions of hypoxia, ischemia, or inflammation. It modulates a variety of physiological functions in many tissues including the brain and heart.^1,2 Adenosine exerts its action via four specific adenosine receptors (also named P1 purinergic receptors): Adenosine A₁ Receptor (A₁AR), Adenosine A_2A Receptor (A_2AAR), Adenosine A_2B Receptor (A_2BAR), and Adenosine A₃ Receptor (A₃AR). The various adenosine receptors can be distinguished on the basis of their distinct molecular structures, distinct tissue distributions, and differential selectivity for adenosine analogs.^1-4 All are integral membrane proteins and are members of the G protein-coupled receptor superfamily. They share a common structure of seven putative transmembrane domains, an extracellular amino terminus, a cytoplasmic carboxyl terminus, and a third intracellular loop important in binding G proteins.^1-3

Expression of A₃AR has been reported in the brain, kidney, liver, and heart. It plays a role in modulation of cerebral ischemia, asthma, and cell growth. In addition, recent studies have established a cardioprotective role for A₃AR.⁵ Expression of A₃AR was reported to be elevated in cancerous tissues as well as in auto-immune inflammatory diseases.^6,7 A patent has been filed for the use of A₃AR and A₃AR agonist as a diagnostic marker for therapeutic treatments of cancer and other diseases.