title: Current knowledge on the role of P2Y receptors in cardioprotection against ischemia-reperfusion.
abstract: During ischemia, numerous effective endogenous extracellular mediators have been identified, particularly, nucleosides such as adenosine as well as purinergic and pyrimidinergic nucleotides. They may play important regulatory roles within the cardiovascular system and notably as cardio-protectants. Indeed, the distribution of the P2Y receptors in mammalian heart includes several cellular constituents relevant for the pathophysiology of myocardial ischemia. Beside the well-known cardioprotective effect of adenosine, the additional protective role of P2Y receptors has emerged. However, interpretation of experimental results may be sometimes perplexing. This is due to the variability of: the experimental models, the endpoints criteria, the chemical structure of agonist and antagonist ligands and their concentrations, the sequences of drug administration with respect to the model used (before and/or during and/or after ischemia). The net effect may be in the opposite direction after a transient or a prolonged stimulation. Nevertheless, the overall reading of published data highlights the beneficial role of the P2Y2/4receptor stimulation, the useful and synergistic role of P2Y6/11receptor activation and even of the P2Y11receptor alone in cardioprotection. More, the P2Y11receptor could be involved in counter-regulation of profibrotic processes. Paradoxically, transient P2X7receptor stimulation could contribute to the net cardioprotective effect of ATP. Recently, experimental data have shown that blocking the P2Y12receptor after ischemia confers cardioprotection independently of platelet antiaggregatory effect. This suggests for P2Y receptors an important role in primary prevention and as a therapeutic target in myocardial protection during ischemia and reperfusion.
authors: Department of Pharmacology, E.A.3801, SFR CAP-santé, Reims University Hospital, 51, rue Cognacq-Jay, 51095 Reims Cedex, France. Electronic address: zoubir.djerada@univ-reims.fr.
authors: Zoubir
authors: Z
authors: Djerada
authors: Department of Pharmacology, E.A.3801, SFR CAP-santé, Reims University Hospital, 51, rue Cognacq-Jay, 51095 Reims Cedex, France.
authors: Catherine
authors: C
authors: Feliu
authors: Inserm (Institut National de la Santé et de la Recherche Médicale) U1096, Department of Pharmacology, Rouen, France; Normandy University, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors: Vincent
authors: V
authors: Richard
authors: Department of Pharmacology, E.A.3801, SFR CAP-santé, Reims University Hospital, 51, rue Cognacq-Jay, 51095 Reims Cedex, France.
authors: Hervé
authors: H
authors: Millart
mesh_terms: D002118:Calcium / Q000378:metabolism; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058470:Receptors, Purinergic P2Y / Q000502:physiology*; D015398:Signal Transduction; D014544:Uridine Triphosphate / Q000502:physiology
chemical_list: C109734:P2RY11 protein, human; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; C104749:purinoceptor P2Y4; D002118:Calcium; D014544:Uridine Triphosphate
keywords: Cardioprotection; Ischemia/reperfusion; P2X(7); P2Y receptor