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首页> 外文期刊>The European Journal of Neuroscience >μ-Opioid receptor desensitization: Homologous or heterologous?
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μ-Opioid receptor desensitization: Homologous or heterologous?

机译：μ阿片受体脱敏：同源还是异源？

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There is considerable controversy over whether μ-opioid receptor (MOPr) desensitization is homologous or heterologous and over the mechanisms underlying such desensitization. In different cell types MOPr desensitization has been reported to involve receptor phosphorylation by various kinases, including G-protein-coupled receptor kinases (GRKs), second messenger and other kinases as well as perturbation of the MOPr effector pathway by GRK sequestration of G protein βγ subunits or ion channel modulation. Here we report that in brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (5-8 weeks old) rapid MOPr desensitization induced by the high-efficacy opioid peptides methionine enkephalin and DAMGO was homologous and not heterologous to α2-adrenoceptors and somatostatin SST2 receptors. Given that these receptors all couple through G proteins to the same set of G-protein inwardly rectifying (GIRK) channels it is unlikely therefore that in mature neurons MOPr desensitization involves G protein βγ subunit sequestration or ion channel modulation. In contrast, in slices from immature animals (less than postnatal day 20), MOPr desensitization was observed to be heterologous and could be downstream of the receptor. Heterologous MOPr desensitization was not dependent on protein kinase C or c-Jun N-terminal kinase activity, but the change from heterologous to homologous desensitization with age was correlated with a decrease in the expression levels of GRK2 in the LC and other brain regions. The observation that the mechanisms underlying MOPr desensitization change with neuronal development is important when extrapolating to the mature brain results obtained from experiments on expression systems, cell lines and immature neuronal preparations. There is considerable controversy over whether rapid mu-opioid receptor (MOPr) desensitization is homologous or heterologous. Here we report that MOPr desensitization is largely homologous in brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (6-8 weeks old) but is heterolgous to α2-adrenoceptors in slices from immature animals (P 20 days). Homologous desensitization with age was correlated with a decrease in the expression levels of GRK2 in the LC and other brain regions. The observation that the mechanisms underlying MOPr desensitization change with neuronal development is important when extrapolating to the mature brain results obtained from experiments on expression systems, cell lines and immature neuronal preparations.
机译：关于μ阿片受体（MOPr）脱敏是同源还是异源以及引起这种脱敏的机制存在很大争议。在不同的细胞类型中，据报道MOPr脱敏涉及各种激酶的受体磷酸化，包括G蛋白偶联受体激酶（GRKs），第二信使和其他激酶，以及通过GRK螯合G蛋白βγ干扰MOPr效应子途径。亚基或离子通道调制。在这里，我们报道在由相对成熟的大鼠（5至8周龄）制备的脑干位点蓝斑（LC）神经元中，由高效阿片肽甲硫氨酸脑啡肽和DAMGO诱导的快速MOPr脱敏与α2-肾上腺素能受体和生长抑素不是同源的SST2受体。考虑到这些受体全部通过G蛋白偶联到同一组G蛋白内向整流（GIRK）通道，因此在成熟神经元中MOPr脱敏不太可能涉及G蛋白βγ亚基螯合或离子通道调节。相反，在未成熟动物的切片中（少于出生后第20天），观察到MOPr脱敏是异源的，并且可能在受体的下游。异源MOPr脱敏不依赖于蛋白激酶C或c-Jun N端激酶活性，但是随着年龄的增长从异源脱敏到同源脱敏的变化与LC和其他脑区域GRK2表达水平的降低有关。从表达系统，细胞系和未成熟神经元制剂的实验中推断出成熟的大脑结果时，观察到MOPr脱敏机制随着神经元的发展而变化的机制非常重要。关于快速阿片受体（MOPr）脱敏是同源还是异源，存在很大争议。在这里，我们报告说，从相对成熟的大鼠（6-8周大）制备的脑干轨迹蓝绿色（LC）神经元中，MOPr脱敏在很大程度上是同源的，但对于未成熟动物的切片中的α2-肾上腺素受体而言，异源性（P <20天）。年龄的同源脱敏与LC和其他脑区域中GRK2表达水平的降低有关。从表达系统，细胞系和未成熟神经元制剂的实验中推断出成熟的大脑结果时，观察到MOPr脱敏的潜在机制随神经元发育而变化的观点很重要。

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