Opioid regulation of mu receptor internalisation: relevance to the development of tolerance and dependence.
Opioid regulation of mu receptor internalisation: relevance to the development of tolerance and dependence.
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DOI：
10.2174/187152710793361522
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
J. López-Giménez;G. Milligan
中科院分区：
文献类型：
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作者：
J. López-Giménez;G. Milligan
μ阿片样物质受体从细胞表面的内化通常通过受体与高效激动剂配体的结合来实现。然而，在许多情况下，强效镇痛吗啡不能有效地促进内化，这与持续使用吗啡导致耐受性和依赖性的倾向之间是否存在直接联系已经被深入研究。虽然经常被描述为部分激动剂，但这一特征似乎不足以解释吗啡促进μ阿片受体内化的能力差。使用转染的细胞系统和离体/体内模型进行的实验提供了证据，表明当吗啡可以促进μ受体的内化时，耐受性和依赖性的发展减少。虽然这个模型的各个方面是有争议的，这样的观察表明，一些方法，以进一步提高吗啡作为镇痛剂的使用。
Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic.