© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Adenosine, adenosine receptors and myocardial protection
An updated overview
Centre for Experimental Surgery and Anaesthesiology, University of Leuven, 3000 Leuven, Belgium
* Corresponding author, CEHA, University of Leuven, Campus Gasthuisberg, B-3000 Leuven, Belgium. Tel.: +32-16-347-132; fax: +32-16-347-139 kanigula.mubagwa{at}med.kuleuven.ac.be
Adenosine (Ado) accumulates in tissues under metabolic stress. On myocardial cells, the nucleoside interacts with various receptor subtypes (A1, A3, and probably A2A and A2B) that are coupled, via G proteins, to multiple effectors, including enzymes, channels, transporters and cytoskeletal components. Studies using Ado receptor agonists and antagonists, as well as animals overexpressing the A1 receptor indicate that Ado exerts anti-ischemic action. Ado released during preconditioning (PC) by short periods of ischemia followed by reperfusion induces cardioprotection to a subsequent sustained ischemia. This protective action is mediated by A1 and A3 receptor subtypes and involves the activation and translocation of PKC to sarcolemmal and to mitochondrial membranes. PKC activation leads to an increased opening of ATP-sensitive K+ (KATP) channels. Recent studies implicate mitochondrial rather than sarcolemmal KATP channels in the protective action of PC. Other effectors possibly contributing to cardioprotection by Ado or PC, and which seem particularly involved in the delayed (second window of) protection, include MAP kinases, heat shock proteins and iNOS. Because of its anti-ischemic effects, Ado has been tested as a protective agent in clinical interventions such as PTCA, CABG and tissue preservation, and was found in most cases to enhance the post-ischemic recovery of function. The mechanisms underlying the role of Ado and of mitochondrial function in PC are not completely clear, and uncertainties remain concerning the role played by newly identified potential effectors such as free radicals, the sarcoplasmic reticulum, etc. In addition, more studies are needed to clarify the signalling mechanisms by which A3 receptor activation or overexpression may promote apoptosis and cellular injury, as reported by a few recent studies.
KEYWORDS Adenosine; Ion channels; Ischemia; Preconditioning; Receptors; Signal transduction
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