ATP and Adenosine Signal Transductions

This chapter focuses on the purine nucleoside, adenosine, and purine nucleotide, adenosine 5'-triphosphate (ATP), which are found in every cell of the human body where they play a critical role in cellular energetics and metabolism. Adenosine and ATP exert a wide spectrum of effects in various tissues and organs other than the heart and are now considered as endogenous physiologic regulators. Both compounds are released into the extracellular space under physiologic conditions and pathophysiologic conditions characterized by an imbalance between oxygen supply and oxygen demand. Other potential sources of extracellular ATP are UTP, via transphosphorylation, and diadenosine polyphosphates, via degradation. Extracellular ATP is degraded to AMP and adenosine by ectoenzymes. Extracellular adenosine acts as a local physiological regulator in the cardiovascular system by interacting with at least four subtypes of cell surface receptors coupled to various signal transduction pathways. Extracellular adenosine exerts negative chronotropic, dromotropic, and inotropic effects and anti-β-adrenergic action in the heart and vasodilatory action on blood vessels. Extracellular ATP exerts pronounced effects in the mammalian heart under physiological and pathophysiological conditions. These include positive or negative inotropic and chronotropic effects mediated mainly by P2Y receptors. Under specific experimental conditions, ATP induces acidosis, cell depolarization, and arrhythmias mostly by acting through P2X receptors.