Role of Intracellular Calcium and Cyclic Nucleotides in Realization of Cardioprotective Effects of delta- and kappa_1-Opioid Receptor Agonists

摘要

The role of cyclic nucleotides (cAMP, cGMP) and Ca~(2+)-ATPase of the sarcoplasmic reticulum in the mechanism of cardioprotective effects of selective delta_1- and kappa_1-opioid receptor agonists DPDPE and U-50488 was studied under conditions of global ischemia and reperfusion of isolated and perfused rat heart. Activation of both types of opioid receptors 2-fold reduced the reperfusion release of creatine phosphokinase. The cardioprotective effect of U-50488 was paralleled by a 2-fold decrease in cAMP content in the myocardium, while DPDPE did not modify the content of cAMP throughout the experiment. None of these substances changed the content of cGMP in the myocardium. The cardioprotective effect of DPDPE was not observed after inhibition of sarcoplasmic reticulum Ca~(2+)-ATPase with cyclopiazonic acid. The cardioprotective effect of U-50488 was associated with reduction of cAMP level in the myocardium, while the cytoprotective effect of DPDPE was mediated by opioidergic modulation of Ca~(2+) transport at the level of the sarcoplasmic reticulum.