Internalization and down-regulation of mu opioid receptors by endomorphins and morphine in SH-SY5Y human neuroblastoma cells
Internalization and down-regulation of mu opioid receptors by endomorphins and morphine in SH-SY5Y human neuroblastoma cells
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DOI：
10.1016/j.brainres.2004.07.055
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发表时间：
2004-12-03
期刊：
影响因子：
2.9
通讯作者：
Zadina, JE
中科院分区：
文献类型：
--
作者：
Horner, KA;Zadina, JE
采用人神经母细胞瘤细胞系SH-SY 5 Y，研究吗啡和内源性阿片肽内吗啡肽-1（EM-1）和内吗啡肽-2（EM-2）对μ阿片受体（莫尔）内化和下调的影响。用100 nM、1 μ M和10 μ M的EM-1、EM-2或吗啡处理24 h，导致μ受体的剂量依赖性下调。将细胞暴露于10 μ M EM-1 2.5、5和24小时导致μ受体的时间依赖性下调。吗啡和EM-1对mu受体的下调作用可被高渗蔗糖阻断，这与内吞依赖性机制一致。用放射性标记的μ拮抗剂进行的敏感的细胞表面结合研究表明，吗啡能够诱导SH-SY 5 Y细胞中天然表达的μ受体的内化。EM-1产生了更迅速的intertemalization μ受体比吗啡，但高渗蔗糖阻断这些激动剂诱导的内化。这项研究表明，与吗啡一样，内吗啡肽以剂量和时间依赖性方式下调μ阿片受体。本研究还表明，吗啡，以及EM-1，可以诱导快速，内吞依赖性的μ阿片受体在SH-SY 5 Y细胞的内化。这些结果可能有助于阐明mu激动剂调节其受体数量和反应性的能力。由爱思唯尔公司出版
The human neuroblastoma cell line, SH-SY5Y, was used to examine the effects of morphine and the endogenous opioid peptides, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), on mu opioid receptor (MOR) internalization and down-regulation. Treatment for 24 h withEM-1, EM-2 ormorphine at 100 nM, 1 muM and 10 muM resulted in a dose-dependent down-regulation of mu receptors. Exposure of cells to 10 muM EM-1 for 2.5, 5 and 24 h resulted in a time-dependent down-regulation of mu receptors. Down-regulation of mu receptors by morphine and EM-1 was blocked by treatment with hypertonic sucrose, c onsistent with an endocytosis-dependent mechanism. Sensitive cell-surface binding studies with a radiolabeled mu antagonist revealed that morphine was able to induce internalization of mu receptors naturally expressed in SH-SY5Y cells. EM-1 produced a more rapid intemalization of mu receptors than morphine, but hypertonic sucrose blocked the internalization induced by each of these agonists. This study demonstrates that, like morphine, the endomorphins down-regulate mu opioid receptors in a dose- and time-dependent manner. This study also demonstrates that morphine, as well as EM-1, can induce rapid, endocytosisdependent internalization of mu opioid receptors in SH-SY5Y cells. These results may help elucidate the ability of mu agonists to regulate the number and responsiveness of their receptors. Published by Elsevier B.V.