Altered expression of P2Y2 and P2X7 purinergic receptors in the isolated rat heart mediates ischemia-reperfusion injury

Vascul Pharmacol. 2015 Oct:73:96-103. doi: 10.1016/j.vph.2015.06.003. Epub 2015 Jun 10.

Abstract

The aim of this study is to analyze the expression of purinergic receptors in the heart after ischemia-reperfusion, and their possible role in ischemia-reperfusion injury. Rat hearts were perfused according to the Langendorff technique and subjected to 30 min ischemia followed by 15 min reperfusion. Ischemia-reperfusion reduced the gene expression and protein content of purinergic receptors of the P2Y2 subtype, and increased the gene expression and protein content of the P2X7 subtype. Treatment with the agonist of the P2Y2 subtype 2-thio-UTP and with the antagonist of the P2X7 subtype Brilliant Blue improved myocardial function parameters, reduced cell death and increased the myocardial expression of antiapoptotic markers after ischemia-reperfusion. These results suggest that the myocardial expression of the protective P2Y2 subtype of purinergic receptors is reduced, whereas that of the harmful subtype P2X7 subtype is increased during coronary ischemia-reperfusion. This may contribute to myocardial injury in this condition.

Keywords: Ischemia–reperfusion; Langendorff; P2Y2, P2X7; Purinergic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Down-Regulation
  • Hemodynamics
  • Isolated Heart Preparation
  • Male
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Purinergic P2X Receptor Antagonists / pharmacology
  • Purinergic P2Y Receptor Agonists / pharmacology
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X7 / drug effects
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / metabolism*
  • Receptors, Purinergic P2Y2 / drug effects
  • Receptors, Purinergic P2Y2 / genetics
  • Receptors, Purinergic P2Y2 / metabolism*
  • Signal Transduction
  • Time Factors
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • P2rx7 protein, rat
  • P2ry2 protein, rat
  • Purinergic P2X Receptor Antagonists
  • Purinergic P2Y Receptor Agonists
  • Receptors, Purinergic P2X7
  • Receptors, Purinergic P2Y2