Protection of cardiac myocytes via delta(1)-opioid receptors, protein kinase C, and mitochondrial K(ATP) 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 microM) 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.
Huh
J
J
Cardiovascular Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
Gross
G J
GJ
Nagase
H
H
Liang
B T
BT
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001597:Benzylidene Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007511:Ischemia / Q000473:pathology; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D010617:Phenanthridines; D026902:Potassium Channel Blockers; D011804:Quinolines; C094142:TAN 67; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; D000255:Adenosine Triphosphate; C016299:chelerythrine; D011493:Protein Kinase C; D005905:Glyburide