Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation.
Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation.
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DOI：
10.1074/jbc.270.51.30290
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发表时间：
1995-12
期刊：
影响因子：
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通讯作者：
G. Stefano;A. Hartman;T. Bilfinger;H. Magazine;H. Magazine;Yu Liu;F. Casares;M. Goligorsky
中科院分区：
文献类型：
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作者：
G. Stefano;A. Hartman;T. Bilfinger;H. Magazine;H. Magazine;Yu Liu;F. Casares;M. Goligorsky
阿片受体最初局限于神经系统，最近已扩大到其他几种细胞类型。基于吗啡的良好的镇静作用，我们假设内皮细胞可能是这种阿片物质的靶点。内皮细胞（人动脉和大鼠微血管）含有高亲和力、可饱和的阿片类药物结合位点，推测其介导吗啡效应，纳洛酮可立体选择性地拮抗吗啡效应。该阿片样物质特异性结合位点对阿片肽不敏感。因此，它被认为是阿片受体的相同亚型（命名为μ 3），用于在表现出相同结合特征的其他细胞类型中介导吗啡。体外培养的内皮细胞和大鼠主动脉环的实验表明，吗啡对内皮细胞的活动产生直接的调节控制，从而导致血管舒张。它诱导一氧化氮的产生，这是一个对纳洛酮拮抗作用和一氧化氮合酶抑制敏感的过程。与阿片类药物相比，阿片肽的给药不会诱导内皮细胞产生一氧化氮。总之，上述数据揭示了吗啡作用的一个新位点，即内皮细胞，其中mu3受体与一氧化氮释放和血管舒张偶联。
Initial confinement of opiate receptors to the nervous system has recently been broadened to several other cell types. Based on the well established hypotensive effect of morphine, we hypothesized that endothelial cells may represent a target for this opiate substance. Endothelial cells (human arterial and rat microvascular) contain a high affinity, saturable opiate binding site presumed to mediate the morphine effects that is stereoselectively and characteristically antagonized by naloxone. This opiate alkaloid-specific binding site is insensitive to opioid peptides. It is, therefore, considered to be the same subtype of opiate receptor (designated mu3) used in the mediation of morphine in other cell types exhibiting the same binding profile. Experiments with endothelial cultures and the aortic ring of rats cultured in vitro demonstrate that morphine exerts direct modulatory control over the activities of endothelial cells, which leads to vasodilation. It induces the production of nitric oxide, a process that is sensitive to naloxone antagonism and nitric oxide synthase inhibition. In contrast with that of opiates, the administration of opioid peptides does not induce nitric oxide production by endothelial cells. In conclusion, the data presented above reveal a novel site of morphine action, endothelial cells, where a mu3 receptor is coupled to nitric oxide release and vasodilation.