Adenosine Receptors in the Heart

Abstract

A1 and A2 adenosine receptors (A1AR, A2AR) mediate the biological actions of this nucleoside. The ligand-binding peptide of the A1AR has an Mr of 35–38 kd and that of the A2AR an Mr of 45 kd. Both are glycoproteins. Alkylxanthines, such as theophylline, competitively inhibit ligand binding at both receptors. GTP-binding transduction proteins couple the receptors to their effectors, Gi (and Go?) for the A1AR and Gs for the A2AR. Effectors which are known to be coupled to cardiac A1ARs include adenylate cyclase (inhibition), muscarinic K+ channels (activation), and ATP-sensitive K+ channels (activation). A1ARs coupled to phospholipase C apparently do not occur in the heart. Stimulation of adenylate cyclase is the only known effect of A2AR activation. Adenosine, formed in the heart and acting through A1ARs coupled to K+ channels, slows the rate of SA node firing, retards conduction through the AV node, and reduces the force of atrial but not ventricular contraction. Acting through A1ARs coupled to adenylate cyclase, adenosine antagonizes the cardiostimulatory actions of catecholamines and other agonists that stimulate cyclic AMP production. A2ARs in the coronary arteries mediate vasodilation. One source of adenosine is cytosolic AMP, linked through myokinase to the cytosolic ATP phosphorylation potential, an index of cellular energy state. Adenosine from this source is thought to couple coronary blood flow rate to the cellular energy state, thus constituting the metabolic component of coronary flow control. The actions of adenosine at cardiac muscle A1ARs tend to reduce energy consumption, whereas the action at coronary A2ARs increases energy supply. In concert, these actions are cardioprotective.