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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons.
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Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons.

机译：吗啡在伏伏核神经元的树突中选择性地急性调节阿片受体的运输。

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Morphine stimulates the internalization of mu-opioid receptors (MORs) in transfected cell models to a lesser degree than opioid peptides and other analgesic drugs, such as methadone, and previous studies have reported that morphine does not produce a detectable redistribution of MORs in neural tissue after either acute or chronic administration. Nevertheless, morphine produces profound physiological effects, raising the question of whether receptor trafficking plays any role in the in vivo actions of morphine. We investigated the effects of opiate drugs on recombinant and native opioid receptors in the nucleus accumbens, which plays an important role in mediating the behavioral effects of opiate drugs. Morphine and methadone differed in their effects on the internalization of epitope-tagged MORs in cell bodies, introduced by viral gene transfer and imaged by fluorescence microscopy. A mutation of the cytoplasmic tail that confers morphine-induced internalization in cultured cells had a similar effect on receptor trafficking in nucleus accumbens cell bodies. Surprisingly, in contrast to its failure to affect MOR distribution detectably in cell bodies, acute morphine administration produced a pronounced change in MOR distribution visualized in the processes of the same neurons. A similar effect of acute morphine administration was observed for endogenously expressed MORs by immunoelectron microscopy; the acute administration of morphine increased the density of MORs associated with internal membrane structures specifically in dendrites. These results provide the first evidence that morphine regulates the distribution of MORs in neuronal processes, suggesting that "compartment-selective" membrane trafficking represents a previously unanticipated type of opioid receptor regulation contributing to the in vivo effects of opiate drugs on a physiologically relevant population of CNS neurons.
机译：吗啡比转染了阿片肽和其他止痛药（如美沙酮）时，在转染的细胞模型中刺激多阿片受体（MOR）的内在化程度，并且先前的研究报道吗啡在神经组织中不会产生可检测到的MORs重新分布急性或慢性给药后。然而，吗啡产生了深远的生理作用，从而引发了一个问题，即受体运输是否在吗啡的体内作用中发挥任何作用。我们调查了阿片药物对伏伏核中重组和天然阿片受体的影响，这在介导阿片药物的行为影响中起着重要作用。吗啡和美沙酮在通过病毒基因转移引入并通过荧光显微镜成像对细胞体中表位标记的MORs的内在化作用方面有所不同。在培养细胞中赋予吗啡诱导的内在化作用的细胞质尾部突变，对伏伏核细胞体中的受体转运具有类似的作用。出人意料的是，与未能在细胞体内可检测地影响MOR分布相反，急性吗啡给药在相同神经元的过程中可见的MOR分布发生了明显变化。通过免疫电子显微镜观察到内源表达的MORs有急性吗啡给药的类似作用。急性给予吗啡会增加与树突内部膜结构相关的MOR的密度。这些结果提供了吗啡在神经元过程中调节MORs分布的第一个证据，表明“区室选择性”膜运输代表了阿片类药物受体调控的先前未曾预料到的类型，这有助于鸦片药物对生理相关人群的体内作用。 CNS神经元。

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