[Intracellular mechanisms of opioidergic regulation of the myocardial function during normoxia and postischemic reperfusion].
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.
Lasukova
T V
TV
Maslov
L N
LN
Gorbunov
A C
AC
Tsibul'nuikov
S Iu
SIu
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003402:Creatine Kinase / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
D002316:Cardiotonic Agents; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D000242:Cyclic AMP; D003402:Creatine Kinase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases