Regulation of opioid receptor trafficking and morphine tolerance by receptor oligornerization
Regulation of opioid receptor trafficking and morphine tolerance by receptor oligornerization
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DOI：
10.1016/s0092-8674(02)00613-x
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发表时间：
2002-01-25
期刊：
影响因子：
64.5
通讯作者：
Whistler, JL
中科院分区：
文献类型：
--
作者：
He, L;Fong, J;Whistler, JL
吗啡用于治疗慢性疼痛的效用因对该药物镇痛作用产生耐受性而受到阻碍。吗啡在阿片类药物中的独特之处在于它能够激活μ阿片受体（MOR）而不促进其脱敏和内吞作用。在这里，我们证明[D-Ala(2)-MePhe(4)-Gly(5)-ol]脑啡肽(DAMGO)可以促进吗啡刺激MOR内吞作用的能力。因此，与单独使用吗啡治疗的大鼠相比，长期使用这两种药物治疗的大鼠表现出镇痛耐受性降低。这些结果表明，MOR 的内吞作用可以减少耐受性的产生，因此提出了一种开发阿片类似物的方法，以增强治疗慢性疼痛的功效。
The utility of morphine for the treatment of chronic pain is hindered by the development of tolerance to the analgesic effects of the drug. Morphine is unique among opiates in its ability to activate the mu opioid receptor (MOR) without promoting its desensitization and endocytosis. Here we demonstrate that [D-Ala(2)-MePhe(4)-Gly(5)-ol] enkephalin (DAMGO) can facilitate the ability of morphine to stimulate MOR endocytosis. As a consequence, rats treated chronically with both drugs show reduced analgesic tolerance compared to rats treated with morphine alone. These results demonstrate that endocytosis of the MOR can reduce the development of tolerance, and hence suggest an approach for the development of opiate analogs with enhanced efficacy for the treatment of chronic pain.