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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)