[Role of kappa1 opioid receptors and cAMP in regulation of cardiac tolerance to ischemia and reperfusion].

Abstract

The cardioprotective, inotropic, and antiarrhythmic effects of U-50.488, a selective agonist of kappa1 opioid receptors (kappa1 ORs), was studied using the model of 45-min total ischemia and 30-min reperfusion of isolated rat heart. Cardiac kappa1 ORs were stimulated by adding U-50.488 to the perfusing solution up to the final concentration of 0.1 or 1 micromol/l. The opioid had no influence on the incidence of reperfusion arrhythmias. The addition of 0.1 micromol/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 micromol/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 kappa1 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 micromol/l) is accounted for by its interaction with unknown nonopioid receptors of cardiac myocytes.

• Authors: T V Lasukova, L N Maslov, A A Platonov, N V Guzarova, Iu B Lishmanov
• Journal: Izvestiia Akademii nauk. Seriia biologicheskaia (Izv Akad Nauk Ser Biol) 2008 Mar-Apr Issue 2 Pg. 223-31 ISSN: 1026-3470 [Print] Russia (Federation)
• PMID: 18946995 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Antihypertensive Agents
• Receptors, Opioid, kappa
• kappa(1) opioid receptor
• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
• Cyclic AMP
• Creatine Kinase

Topics

• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Antihypertensive Agents (pharmacology)
• Creatine Kinase (metabolism)
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Male
• Myocardial Ischemia (metabolism)
• Rats
• Rats, Wistar
• Receptors, Opioid, kappa (antagonists & inhibitors, metabolism)
• Reperfusion