Intracerebroventricular Administration of Morphine Confers Remote Cardioprotection--Role of Opioid Receptors and Calmodulin

Eur J Pharmacol. 2011 Apr 10;656(1-3):74-80. doi: 10.1016/j.ejphar.2011.01.027. Epub 2011 Feb 1.


The current study aimed to delineate the mechanism of remote preconditioning by intracerebroventricular morphine (RMPC) against myocardial ischemia-reperfusion injury. Male Sprague-Dawley rats were given an intracerebroventricular morphine injection before myocardial ischemia and reperfusion injury. Ischemia-reperfusion injury was achieved by 30min of left coronary artery occlusion followed by 120min of reperfusion. The effects of remote preconditioning by intracerebroventricular morphine preconditioning were also determined upon selective blockade of the δ, κ or μ-opioid receptors, or calmodulin (CaM). The infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. Remote preconditioning by intracerebroventricular morphine reduced infarct size in the ischemic/reperfused myocardium, and the effect was abolished by the selective blockade of any one of the three δ, κ and μ opioid receptors or CaM. Furthermore, remote preconditioning by intracerebroventricular morphine increased the expression of CaM in the hippocampus and the plasma level of calcitonin gene-related peptide (CGRP). The results of the present study provide evidence that the cardioprotection of remote preconditioning by intracerebroventricular morphine involves not only all three types of opioid receptors in the central nervous system, but also CaM, which releases CGRP, one of the mediators of remote preconditioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / blood
  • Calmodulin / antagonists & inhibitors
  • Calmodulin / metabolism*
  • Cardiotonic Agents / administration & dosage*
  • Cardiotonic Agents / pharmacology*
  • Cerebral Infarction / blood
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / pathology
  • Cerebral Infarction / prevention & control
  • Cerebral Ventricles* / blood supply
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Ischemic Preconditioning
  • Male
  • Morphine / administration & dosage*
  • Morphine / pharmacology*
  • Narcotic Antagonists
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / metabolism*
  • Reperfusion Injury / blood
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control


  • Calmodulin
  • Cardiotonic Agents
  • Narcotic Antagonists
  • Receptors, Opioid
  • Morphine
  • Calcitonin Gene-Related Peptide