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首页> 外文期刊>The European Journal of Neuroscience >Role of protein kinase C and mu-opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons.
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Role of protein kinase C and mu-opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons.

机译：蛋白激酶C和μ阿片受体（MOPr）脱敏在大鼠蓝绿色神经元对吗啡的耐受性中的作用。

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摘要

In morphine tolerance a key question that remains to be answered is whether mu-opioid receptor (MOPr) desensitization contributes to morphine tolerance, and if so by what cellular mechanisms. Here we demonstrate that MOPr desensitization can be observed in single rat brainstem locus coeruleus (LC) neurons following either prolonged (> 4 h) exposure to morphine in vitro or following treatment of animals with morphine in vivo for 3 days. Analysis of receptor function by an operational model indicated that with either treatment morphine could induce a profound degree (70-80%) of loss of receptor function. Ongoing PKC activity in the MOPr-expressing neurons themselves, primarily by PKCalpha, was required to maintain morphine-induced MOPr desensitization, because exposure to PKC inhibitors for only the last 30-50 min of exposure to morphine reduced the MOPr desensitization that was induced both in vitro and in vivo. The presence of morphine was also required for maintenance of desensitization, as washout ofmorphine for > 2 h reversed MOPr desensitization. MOPr desensitization was homologous, as there was no change in alpha(2)-adrenoceptor or ORL1 receptor function. These results demonstrate that prolonged morphine treatment induces extensive homologous desensitization of MOPrs in mature neurons, that this desensitization has a significant PKC-dependent component and that this desensitization underlies the maintenance of morphine tolerance.
机译：在吗啡耐受性中，仍有待回答的关键问题是μ阿片受体（MOPr）脱敏是否有助于吗啡耐受性，以及是否通过什么细胞机制起作用。在这里，我们证明了在长时间（> 4 h）体外暴露于吗啡后，或在体内用吗啡处理动物3天后，可以在单个大鼠脑干轨迹蓝绿色（LC）神经元中观察到MOPr脱敏。通过操作模型对受体功能的分析表明，无论哪种处理，吗啡都可能引起很大程度的受体功能丧失（70-80％）。要维持吗啡诱导的MOPr脱敏，主要需要由PKCalpha进行的表达MOPr的神经元本身正在进行的PKC活性，因为仅在暴露于吗啡的最后30-50分钟内暴露于PKC抑制剂会降低MOPr的脱敏，这两者体外和体内。维持脱敏也需要吗啡的存在，因为冲刷2小时以上的吗啡会逆转MOPr脱敏。 MOPr脱敏是同源的，因为alpha（2）-肾上腺素受体或ORL1受体功能没有变化。这些结果表明，延长的吗啡治疗会在成熟神经元中引起MOPrs广泛的同源性脱敏，这种脱敏具有重要的PKC依赖性成分，并且这种脱敏是维持吗啡耐受性的基础。

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