Protection of cardiac myocytes via δ1-opioid receptors, protein kinase C, and mitochondrial KATP channels

The objective of the present study was to investigate the role of delta (1)-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K+ (K-ATP) channels act downstream of the delta (1)-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective delta (1)-opioid receptor agonist (-)-TAN-67 (1 muM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective delta (1)-opioid receptor antagonist, completely blocked the cardioprotective effect of (-)-TAN-67. Naltriben methanesulfonate, a selective delta (2)-opioid receptor antagonist, had only a slight inhibitory effect on (-)-TAN-67- mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a kappa -opioid receptor antagonist, did not affect (-)-TAN- 67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the K-ATP channel inhibitors glibenclamide, a nonselective K-ATP antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective K-ATP antagonist, reversed the cardioprotective effect of (-)-TAN-67. These results suggest that the delta (1)-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial K-ATP channel.