Lishmanov A Yu, Maslov L N, Lasukova T V, Crawford D, Wong T M
Institute of Cardiology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
Bull Exp Biol Med. 2007 Feb;143(2):187-90. doi: 10.1007/s10517-007-0046-6.
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.
用κ-阿片受体拮抗剂（-）-U-50,488（1毫克/千克）进行静脉预处理，可提高心脏对冠状动脉闭塞和再灌注致心律失常作用的抵抗力。选择性κ1-阿片受体拮抗剂诺宾那托啡和外周阿片受体非选择性阻滞剂甲基纳洛酮消除了这种抗心律失常作用。用白屈菜红碱对蛋白激酶C进行初步阻断或用格列本脲抑制ATP依赖性钾通道（KATP通道）消除了κ-阿片受体激活的抗心律失常作用。肌膜KATP通道的选择性抑制剂未调节κ-阿片受体介导的心脏电稳定性增加。我们的结果表明，蛋白激酶C和线粒体KATP通道在与外周κ-阿片受体激活相关的抗心律失常作用中起重要作用。
