3.2  钾离子  在神经细胞，刺激δ受体可激活钾外流。同时还有研究表明，OFQ可以激活K＋通道，增强K＋电导［14］。在心肌细胞，U50,488H也有类似的作用，使动作电位时程缩短。动作电位时程缩短将会使通过L型Ca2＋通道内流的Ca2＋减少，并导致SR对钙的回摄降低，使［Ca2＋］i瞬变幅度下降，心肌收缩力降低。Champion等认为内吗啡肽通过增加细胞膜上钾离子通透性，使钾离子大量外流或抑制钙离子内流使血管平滑肌超极化等方式，来降低血管收缩活性。在大鼠的脑干神经元中，δ阿片受体拮抗剂可抑制G蛋白偶联K＋通道的活性［15］。

　　以上结果证实，激动阿片受体可以通过对［K＋］的影响，改变膜电位，进而产生抑制作用。

　　有实验证实，激动δ受体还可以导致线粒体KATP激活，进而产生KATP在缺血预处理中介导的心肌保护作用［16］。Aitchison的研究工作进一步证明了激动δ1受体导致KATP的激活［17］。KATP通道在一般情况下处于关闭状态，在缺血预处理过程中，刺激阿片受体，使KATP通道激活，则钾离子大量外流，产生了超极化，并引起动作电位时程缩短，从而减小心肌的收缩性，这种能量节约效应，可以延迟因缺少能量而造成的细胞损伤。
阿片样物质在延迟IPC中也有同样的保护作用，这种保护作用同样可以被KATP的非选择性拮抗剂优降糖和线粒体KATP非选择性拮抗剂5-HD所阻断，这表明延迟IPC中激活阿片受体可产生KATP介导的心脏保护作用。

　　Shaker和Armstead证实了激活阿片受体可以产生由KATP介导的血管舒张作用，Armstead于1999年又发现了孤啡肽的血管舒张现象也是由KATP介导的。

　　4  结语

　　综上所述，内源性阿片肽及阿片样物质可以通过影响膜离子通道和细胞内离子浓度产生对心血管系统的抑制效应。对EOP离子机制的研究有助于理解EOP在心血管系统的生理和病理学作用，并为缺血再灌注损伤等疾病的防治提供新的思路［18］。

　　【参考文献】

　　1  毕辉, 朱妙章, 王跃民,等.U50488H对大鼠血压的影响及机制. 医学研究生学报, 2004, 17(5): 404-407.

　　2  Lasukova TV, Maslov LN, Lishmanov IuB, et al. Contribution of delta1-opioid receptors in regulation of cardiac resistance to ischemia-reperfusion. Ross Fiziol Zh Im I M Sechenova, 2002, 88(5): 568-580.

　　3  Valtchanova-Matchouganska A,Missankov A,Ojewole JA. Evaluation of the antidysrhythmic effects of delta- and kappa-opioid receptor agonists and antagonists on calcium chloride-, adrenaline- and ischemia/reperfusion-induced arrhythmias in rats. Methods Find Exp Clin Pharmacol, 2004, 26(1): 31-38.

　　4  Lendeckel U, Muller C, Rocken C, et al. Expression of opioid receptor subtypes and their ligands in fibrillating human atria. Pacing Clin Electrophysiol, 2005, 28(Suppl 1): S275-279.

　　5  Roumy M, Zajac JM. Modulation of calcium conductance by opioid and anti-opioid peptides. J Soc Biol, 2001, 195(3): 277-283.

　　6  Zhang M, Wang X, Zhang D, et al. Orphanin FQ Antagonizes the Inhibition of Ca2+ Currents Induced by micro-Opioid Receptors. J Mol Neurosci, 2005, 25(1): 21-28.

　　7  Yang JC, Shan J, Ng KF, et al. Morphine and methadone have different effects on calcium channel currents in neuroblastoma cells. Brain Res, 2000, 870(1-2): 199-203.

　　8  Kitamura G, Ohta T, Kai T, et al. Inhibitory effects of opioids on voltage-dependent Ca2+ channels and catecholamine secretion in cultured porcine adrenal chromaffin cells. Brain Res, 2002, 942(1-2): 11-22.

　　9  Lasukova TV, Maslov LN, Lishmanov IuB, et al. Contribution of delta1-opioid receptors in regulation of cardiac resistance to ischemia-reperfusion. Ross Fiziol Zh Im I M Sechenova, 2002, 88(5): 568-580.

　　10  Stanfill AA, Jackson K, Farias M, et al. Leucine-enkephalin interrupts sympathetically mediated tachycardia prejunctionally in the canine sinoatrial node. Exp Biol Med (Maywood), 2003, 228(8): 898-906.

　　11  Chieng B, Bekkers JM. Inhibition of calcium channels by opioid- and adenosine-receptor agonists in neurons of the nucleus accumbens. Br J Pharmacol, 2001, 133(3): 337-344.

　　12  Pan ZZ. Kappa-opioid receptor-mediated enhancement of the hyperpolarization-activated current (I(h)) through mobilization of intracellular calcium in rat nucleus raphe magnus. J Physiol, 2003, 548(Pt 3): 765-775.

　　13  Wang X, Dergacheva O, Griffioen KJ, et al. Action of kappa and Delta opioid agonists on premotor cardiac vagal neurons in the nucleus ambiguus. Neuroscience, 2004, 129(1): 235-241.

　　14  Moran TD,Abdulla FA,Smith PA. Cellular neurophysiological actions of nociceptin/orphanin FQ. Peptides, 2000, 21(7): 969-976.

　　15  Shirasaki T, Abe K, Soeda F, et al. delta-Opioid receptor antagonists inhibit GIRK channel currents in acutely dissociated brainstem neurons of rat. Brain Res, 2004, 1006(2): 190-197

　　16  McPherson BC,Yao Z. Morphine mimics preconditioning via free radical signals and mitochondrial K(ATP) channels in myocytes. Circulation, 2001, 103(2): 290-295.

　　17  Aitchison KA,Baxter G F, Awan MM, et al. Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart:implications for ischemic preconditioning. Basic Res Cardiol, 2000, 95(1): 1-10.

　　18  Lasukova TV, Maslov LN, Lishmanov IuB, et al. Contribution of delta1-opioid receptors in regulation of cardiac resistance to ischemia-reperfusion. Ross Fiziol Zh Im I M Sechenova, 2002, 88(5): 568-580.

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