[Intracellular mechanisms of opioidergic regulation of the myocardial function during normoxia and postischemic reperfusion].

Abstract

Cardioprotective and inotropic effects of selective agonists of delta1- and k1-opioid receptors (OR): DPDPE (0.1 microM/L) and U-50.488 (0.1 microM/L) were studied during 45 min global ischemia and 30 min reperfusion of the rat isolated perfused heart. Activation of both OR types promoted a 2-fold reduction in reperfusion leakage of creatine kinase. Cardioprotective effect of U-50.488 was accompanied by a 2-fold decrease in cAMP levels in myocardium. The selective delta1-agonist DPDPE had no effect on the cAMP content. Cardioprotective effect of DPDPE was not demonstrated after inhibition of Ca2+-ATPase in sarcoplasmic reticulum (SR) by cyclopiazonic acid. Stimulation of myocardial delta1- and K1-OR decreased the heart rate and force of contraction both before ischemia and during reperfusion. In summary, cardioprotective effect of U-50.488 depends on the reduction in myocardial cAMP levels whereas cytoprotective effect of DPDPE is mediated via opioidergic alteration in Ca2+-transport at SR level. Decrease in pump function of heart in response to OR activation does not depend upon alteration in cAMP levels in the myocardium.

• Authors: T V Lasukova, L N Maslov, A C Gorbunov, S Iu Tsibul'nuikov
• Journal: Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova (Ross Fiziol Zh Im I M Sechenova) Vol. 95 Issue 4 Pg. 376-86 (Apr 2009) ISSN: 0869-8139 [Print] Russia (Federation)
• PMID: 19505040 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
• Enkephalin, D-Penicillamine (2,5)-
• Cyclic AMP
• Creatine Kinase
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer (pharmacology, therapeutic use)
• Animals
• Cardiotonic Agents (pharmacology, therapeutic use)
• Creatine Kinase (blood)
• Cyclic AMP (metabolism)
• Enkephalin, D-Penicillamine (2,5)- (pharmacology, therapeutic use)
• Heart Rate (drug effects, physiology)
• Male
• Myocardial Contraction (drug effects, physiology)
• Myocardial Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Rats
• Rats, Wistar
• Receptors, Opioid, delta (antagonists & inhibitors, physiology)
• Receptors, Opioid, kappa (antagonists & inhibitors, physiology)
• Sarcoplasmic Reticulum (physiology)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)