Role of κ1 opioid receptors and cAMP in regulation of cardiac tolerance to ischemia and reperfusion

T. V. Lasukova, L. N. Maslov, A. A. Platonov, N. V. Guzarova, Yu B. Lishmanov

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Cardioprotective, inotropic, and antiarrhythmic effects of the selective agonist of κ1 opioid receptors (κ1-ORs) U-50.488H have been studied after 45-min global ischemia and 30-min reperfusion of isolated perfused rat hearts. The heart κ1-ORs were stimulated by adding 0.1 or 1 μmol/l U-50.488H to the perfusion solution. The opioid did not affect the frequency of reperfusion arrhythmias. At a concentration of 0.1 μmol/l, it induced a twofold decrease in the reperfusion release of creatine phosphokinase (CPK), which positively correlated with a decrease in the myocardial cAMP level (r = 0.89, p < 0.01). Application of U-50.488H at a final concentration of 1 μmol/l did not change the cAMP level and CPK release. These results suggest that the cardioprotective effect of U-50.488H is due to a decrease in the level of cAMP in cardiomyocytes. Activation of κ1-ORs decreased the frequency and force of myocardial contractions. It has been shown that the negative inotropic and chronotropic effects of U-50.488H are independent of changes in the myocardial cAMP level. A hypothesis is proposed that the absence of cardioprotective effect of 1μM U-50.488H is a result of activation of nonopioid receptors in cardiomyocytes.

Original languageEnglish
Pages (from-to)499-506
Number of pages8
JournalBiology Bulletin
Volume35
Issue number5
DOIs
Publication statusPublished - 1 Oct 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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