Faculty Collaboration Database

Direct preconditioning of cardiac myocytes via opioid receptors and KATP channels. Circ Res 1999 Jun 25;84(12):1396-400

Date

06/26/1999

Pubmed ID

10381891

DOI

10.1161/01.res.84.12.1396

Scopus ID

2-s2.0-0033603357 (requires institutional sign-in at Scopus site)   165 Citations

Abstract

Previous studies demonstrated that opioid receptor activation mimics the cardioprotective effect of ischemic preconditioning via KATP channels in the intact heart. However, it is unknown whether this beneficial effect is exerted at the level of the cardiac myocyte or coronary vasculature or is mediated via the sarcolemmal or the mitochondrial KATP channel. Thus, the purpose of the present study was to investigate whether opioid receptor stimulation could mimic the cardioprotective effect of preconditioning in a cardiac myocyte model of simulated ischemia. Cardiac ventricular myocytes cultured from chick embryos 14 days in ovo were used as an in vitro model for ischemic preconditioning. A 5-minute exposure of the myocytes to the opioid receptor agonist morphine protected the myocytes during a subsequent 90-minute period of simulated ischemia, which was manifested as a pronounced reduction in the percentage of cardiac cells killed and the amount of creatine kinase released during ischemia. The preconditioning-like effect of morphine was concentration-dependent, reached a maximal effect at 1 micromol/L, and was reversed by naloxone (0.1 to 10 micromol/L). When KATP channel antagonists, such as glibenclamide, or the mitochondrial selective inhibitor 5-hydroxydecanoic acid were present during preexposure to morphine, they abolished the protective effect of morphine. Thus, cardiac myocytes express functional opioid receptors, and their activation mimics the cardioprotective effect of ischemic preconditioning. These results provide direct evidence that the preconditioning-like effect of morphine in the intact heart can be exerted at the level of cardiac myocytes and is most likely the result of mitochondrial KATP channel activation.

Author List

Liang BT, Gross GJ

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Analgesics, Opioid
Animals
Anti-Arrhythmia Agents
Benzylidene Compounds
Cells, Cultured
Chick Embryo
Decanoic Acids
Hydroxy Acids
Ischemic Preconditioning, Myocardial
Morphine
Muscle Fibers, Skeletal
Myocardium
Naloxone
Naltrexone
Narcotic Antagonists
Potassium Channels
Receptors, Opioid