Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase.
Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase.
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Morphine-6beta-glucuronide 调节诱导型一氧化氮合酶的表达。
DOI：
10.1023/a:1010924320902
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发表时间：
2001
期刊：
影响因子：
5.1
通讯作者：
Carrigan,KA
中科院分区：
文献类型：
--
作者：
Lysle,DT;Carrigan,KA
吗啡的免疫调节作用已被公认，然而，令人惊讶的是，对吗啡主要代谢产物的免疫调节特性知之甚少。本研究验证了诱导型一氧化氮合酶（iNOS）的表达受吗啡代谢物吗啡-6 β-葡萄糖醛酸苷调节的假设。使用大鼠进行的初步研究表明，吗啡-6 β-葡糖苷酸给药（0、1.0、3.163、10 mg/kg s.c.）导致脾、肺和肝组织中脂多糖（LPS）诱导的iNOS（诱导型一氧化氮合成酶）表达的显著降低，如通过蛋白质印迹所测量的。吗啡-6 β-葡萄糖醛酸苷还可降低血浆亚硝酸盐/硝酸盐水平，后者是一氧化氮降解的更稳定终产物。在随后的研究中，在注射吗啡-6 β-葡萄糖醛酸苷（10 mg/kg）之前给予阿片受体拮抗剂纳洛酮（0.1 mg/kg）可阻断吗啡-6 β-葡萄糖醛酸苷诱导的iNOS表达和血浆亚硝酸盐/亚硝酸盐水平降低，表明该作用是通过阿片受体介导的。本研究首次提供了吗啡-6 β-葡萄糖醛酸苷改变iNOS表达的证据。
The immunomodulatory effects of morphine are well established; however, suprisingly little is known about the immunomodulatory properties of the major metabolites of morphine. The present study tests the hypothesis that expression of inducible nitric oxide synthase (iNOS) is modulated by the administration of the morphine metabolite, morphine-6β-glucuronide. The initial study using rats shows that morphine-6β-glucuronide administration (0, 1.0, 3.163, 10 mg/kg s.c.) results in a pronounced reduction in lipopolysaccharide (LPS)-induced expression of iNOS (inducible nitricoxide synthease) in spleen, lung, and liver tissue as measured by western blotting. Morphine-6β-glucuronide also produces a reduction in the level of plasma nitrite/nitrate, the more stable end-product of nitric oxide degradation. In a subsequent study, administration of the opioid receptor antagonist, naltrexone (0.1 mg/kg) prior to the injection of morphine-6β-glucuronide (10 mg/kg) blocks the morphine-6β-glucuronide induced reduction of iNOS expression and plasma nitrite/nitrite levels indicating that the effect is mediated via the opioid-receptor. This study provides the first evidence that morphine-6β-glucuronide alters the expression of iNOS.