Adenosine: Advanced pharmacology, basic research and clinical aspects

This chapter discusses the broad spectrum of clinical usage, diagnostic applications, experimental challenges and future perspectives of adenosine. Adenosine, an adenylic nucleotide metabolite, widely distributed throughout the human body, exerts a wide range of regulatory effects. From a cardiovascular perspective, data indicate that the adenosinergic system is important in mediating protection (e.g. via pre- and post-conditioning) and in determining myocardial resistance to insult or to reperfusion-ischemia injury. esides, adenosine exerts its effects through currently four known adenosine receptor (AR) subtypes namely A1R, A2AR, A2BR and A3R. In general, A2AR is thepredominant receptor subtype responsible for coronary blood flow regulation, which dilates coronary arteries. Interestingly, adenosine exerts its cardiac electrophysiologic effects via A1R (e.g. anti-b-adrenergic action). Regarding the supraventricular tissues, adenosine remains as a "first line" harmacologic agent for the treatment of supraventricular arrhythmias, due to its effect on inhibiting rapidly the atrioventricular (AV) nodal conduction. In addition to its clinical role as an antiarrhythmic agent, adenosine has been also administered under conditions of hypoxia, ischemia, and cardiac arrest. Thus, basic research has implicated adenosine as an endogenous distress molecule with essential impact on immune response, adaptation to limited oxygen availability, anti-inflammatory action. Specific AR agonists or antagonists in conjunction with studies in genetic models for adenosine generation have identified a rapidly expanding field of biomedical roles and potential therapeutic applications of extracellular adenosine signaling.