© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Therapeutic receptor targets of ischemic preconditioning
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 USA
ggross{at}mcw.edu
* Corresponding author. Tel.: +1-414-456-8627; fax: +1-414-456-6545
This review focuses on target receptors that have been shown to have the potential to mimic the cardioprotective effect of ischemic preconditioning (IPC). There is an abundance of information concerning the intracellular mechanisms and membrane-bound receptors responsible for IPC. Important intracellular mediators of this cardioprotection likely reside in the activation of multiple kinase cascades. The major players in IPC are thought to include protein kinase C, tyrosine kinases, and members of the mitogen-activated protein kinase signaling family and these topics will be covered in more detail in other papers of this focused issue. However, many of these kinase-mediated mechanisms are triggered by the activation of transmembrane spanning receptors, some of which may be manipulated therapeutically to induce cardioprotection in humans with unstable angina or who are at risk for myocardial infarction. In this review, we will discuss the evidence supporting the possibility of manipulating several of these G protein-coupled receptors as potential therapeutic targets. Stimulation of numerous receptors has been targeted as possible triggers for IPC. Some of those that have been identified include A1 adenosine, 
1 adrenergic, M2 muscarinic, B2 bradykinin, 
1 opioid, AT1 angiotensin, and endothelin-1 receptors. In general, these receptors are thought to couple to inhibitory G proteins. In this review, we will focus on the most likely therapeutic candidates for cardioprotection, namely adenosine, opioid, and bradykinin receptors since selective agonists and antagonists, either alone or in combination, have most often been shown to mimic or block IPC in numerous animal models and man, respectively. This is not meant to completely rule out other receptors since it is clear that IPC is a phenomenon with multiple pathways that appear to be responsible for the cardioprotection observed.
KEYWORDS Adenosine; Infarction; Preconditioning; Receptors