Pharmacology of Adenosine Receptors

Adenosine is an endogenous nucleoside molecule, regulating a myriad of physiological and pathological effects in almost all the organs systems including central nervous system (CNS), cardiovascular system (CVS), respiratory system, renal system, and immune system. Biological functions of adenosine are mediated by its interactions with four subtypes of G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B, and A3 adenosine receptors (ARs) which are ubiquitously present throughout the body. However, ubiquitous distribution of ARs in both healthy and diseased tissues imposed a great challenge to the researchers in the discovery and development of ligands targeting a particular AR subtype in a specific tissue, devoid of undesirable side effects. This chapter provides an overview of the synthesis, metabolism, and cellular transport of adenosine, with particular emphasis on the distribution and signaling mechanisms of ARs, including specific examples of agonists/partial agonists, antagonists, and allosteric modulators of ARs as potential therapeutic agents.