Activation of kappa-opioid receptor as a method for prevention of ischemic and reperfusion arrhythmias: role of protein kinase C and K(ATP) channels.
Intravenous pretreatment with kappa-opioid receptor antagonist (-)-U-50,488 (1 mg/kg) improved heart resistance to the arrhythmogenic effect of coronary occlusion and reperfusion. Selective kappa1-opioid receptor antagonist norbinaltorphimine and nonselective blocker of peripheral opioid receptors methylnaloxone abolished this antiarrhythmic effect. Preliminary blockade of protein kinase C with chelerythrine or inhibition of ATP-dependent K+ channels (K(ATP) channels) with glybenclamide abolished the antiarrhythmic effect of kappa-opioid receptor activation. Selective inhibitor of sarcolemmal K(ATP) channels did not modulate the kappa-opioid receptor-mediated increase in cardiac electrical stability. Our results suggest that protein kinase C and mitochondrial K(ATP) channels play an important role in the antiarrhythmic effect associated with activation of peripheral kappa-opioid receptors.
Lishmanov
A Yu
AY
Institute of Cardiology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
Maslov
L N
LN
Lasukova
T V
TV
Crawford
D
D
Wong
T M
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000494:pharmacology*; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D053119:Benzophenanthridines / Q000008:administration & dosage / Q000494:pharmacology; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D010111:Oxymorphone / Q000008:administration & dosage / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D053119:Benzophenanthridines; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D010111:Oxymorphone; C016299:chelerythrine; D011493:Protein Kinase C; D005905:Glyburide