Pathophysiology and pharmacology of the adenosine system

Purine derivatives, especially adenosine and ATP, play an important role in the function of many organs, being released either as purinergic transmitters or as local modulators in a non-specific way from all tissues. Adenosine and adenine nucleotides act physiologically by interfering with specific cell membrane receptors (P1 and P2 respectively) that are associated with several signal transduction systems. The adenosine system seems to act in complex situations in which cells and tissues must deal with high energy consumption, maintaining or restoring an adequate balance between metabolic requirements and supply. This effect occurs by means of a series of events involving increased blood flow, an improvement in oxygen transport and utilization, as well as a cell protecting and energy saving mechanism. The activity of endogenous adenosine may be pharmacologically affected: a) by blocking cell receptors with methylxanthines or b) by inhibiting the specific cell uptake system and thus increasing interstitial concentration of adenosine and its metabolic half-life. Recently exogenous adenosine has been employed as a drug to induce controlled and stable hypotension during anesthesia, to reduce afterload in various forms of low cardiac output states, to cause platelet preservation during cardiopulmonary bypass and especially to reverse paroxysmal supraventricular tachycardias.