| Abstract: | Adenosine, a naturally-occurring nucleoside, modulates a variety of physiological and pathophysiological processes. The effects of adenosine are mediated via a family of cell surface G-protein-coupled receptors designated into four subtypes, A1, A2A, A2B and A3. The adenosine receptors have widespread tissue distribution and are often co-expressed in the same cell type. Research on adenosine receptors over the past few decades has resulted in the molecular cloning of the four subtypes from multiple species, significant progress in identifying selective agonists and antagonists and an increased understanding of the particular roles adenosine receptor subtypes play in physiological processes. This knowledge has continued to fuel considerable interest in pursuing adenosine receptors as therapeutic targets. For example, adenosine receptor agonists have been proposed for the treatment of heart arrhythmias, inflammatory diseases and in diagnosing coronary artery disease. In general, adenosine receptor agonists are derivatives of the physiological agonist, adenosine. The development of adenosine receptor agonists has been limited by an essential requirement for retention of the ribose moiety for agonist activity. Despite this restriction, significant progress has been made in the identification of potent and selective adenosine receptor agonists, some of which have entered clinical trials. |
