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 journalArticle

Abstract

The cardioprotective, inotropic, and antiarrhythmic effects of U-50.488, a selective agonist of κ1 opioid receptors (κ1 ORs), was studied using the model of 45-min total ischemia and 30-min reperfusion of isolated rat heart. Cardiac κ1 ORs were stimulated by adding U-50.488 to the perfusing solution up to the final concentration of 0.1 or 1 μmol/l. The opioid had no influence on the incidence of reperfusion arrhythmias. The addition of 0.1 μmol/l U-50.488 reduced the reperfusion release of creatine phosphokinase (CPK) by half, which positively correlated with the decrease in the myocardial cAMP content (r = 0.89, p < 0.01). At the same time, the addition of U-50.488 in the higher concentration (1 μmol/l) had no effect on either cAMP level or CPK release. These results indicate that the cardioprotective effect of U-50.488 may be connected with the reduction of myocardial cAMP content. Activation of κ1 ORs caused a decrease in both frequency and amplitude of myocardial contractions. The negative inotropic and chronotropic effect of U-50.488 was shown to be independent of changes in the myocardial cAMP content. A hypothesis is proposed that the absence of any cardioprotective effect of U-50.488 at the higher concentration (1 μmol/l) is accounted for by its interaction with unknown nonopioid receptors of cardiac myocytes.

Original languageEnglish
Pages (from-to)194-201
Number of pages8
JournalBiology Bulletin
Volume35
Issue number2
DOIs
Publication statusPublished - 1 Apr 2008

ASJC Scopus subject areas

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

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