Cardioprotective effect of kappa1-opioid receptor activation and role of cAMP in its realization.
The cardioprotective and antiarrhythmic effects of a selective kappa1-opioid receptor agonist U-50,488 were studied during experimental 45-min total ischemia and 30-min reperfusion of isolated rat heart. The opioid had no effect on the incidence and type of reperfusion arrhythmias. U-50,488 in a concentration of 0.1 microM inhibited reperfusion-induced release of creatine phosphokinase and decreased cAMP concentration in the myocardium by 2 times. These parameters remained unchanged after treatment with U-50,488 in a concentration of 1 microM. The cardioprotective effect of U-50,488 was probably associated with a decrease in cAMP concentration in heart cells. U-50,488 in a concentration of 1 microM produced no cardioprotective effect, which can be explained by its interaction with an unknown non-opioid receptor in cardiomyocytes.
Lasukova
T V
TV
Institute of Cardiology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
Maslov
L N
LN
Platonov
A A
AA
Guzarova
N V
NV
Lishmanov
Yu B
YB
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000517:prevention & control*; D003402:Creatine Kinase / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D017473:Receptors, Opioid, kappa; C116587:kappa(1) opioid receptor; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000242:Cyclic AMP; D003402:Creatine Kinase