Protection of cardiac myocytes via d1-opioid receptors, protein kinase C, and mitochondrial KATP channels

Huh, Joon, Garrett J. Gross, Hiroshi Nagase, and Bruce T. Liang. Protection of cardiac myocytes via d1-opioid receptors, protein kinase C, and mitochondrial KATP channels. Am J Physiol Heart Circ Physiol 280: H377–H383, 2001.—The objective of the present study was to investigate the role of d1-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K (KATP) channels act downstream of the d1-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective d1-opioid receptor agonist (2)-TAN-67 (1 mM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective d1-opioid receptor antagonist, completely blocked the cardioprotective effect of (2)-TAN-67. Naltriben methanesulfonate, a selective d2-opioid receptor antagonist, had only a slight inhibitory effect on (2)-TAN67-mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a k-opioid receptor antagonist, did not affect (2)TAN-67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the KATP channel inhibitors glibenclamide, a nonselective KATP antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective KATP antagonist, reversed the cardioprotective effect of (2)-TAN-67. These results suggest that the d1-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial KATP channel.