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首页> 外文期刊>The European Journal of Neuroscience >Regulation of RGS proteins by chronic morphine in rat locus coeruleus.
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Regulation of RGS proteins by chronic morphine in rat locus coeruleus.

机译：慢性吗啡对大鼠蓝斑中RGS蛋白的调节。

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摘要

The present study explored a possible role for RGS (regulators of G protein signalling) proteins in the long term actions of morphine in the locus coeruleus (LC), a brainstem region implicated in opiate physical dependence and withdrawal. Morphine influences LC neurons through activation of micro -opioid receptors, which, being Gi/o-linked, would be expected to be modulated by RGS proteins. We focused on several RGS subtypes that are known to be expressed in this brain region. Levels of mRNAs encoding RGS2, -3, -4, -5, -7, -8 and -11 are unchanged following chronic morphine, but RGS2 and -4 mRNA levels are increased 2-3-fold 6 h following precipitation of opiate withdrawal. The increases in RGS2 and -4 mRNA peak after 6 h of withdrawal and return to control levels by 24 h. Immunoblot analysis of RGS4 revealed a striking divergence between mRNA and protein responses in LC: protein levels are elevated twofold following chronic morphine and decrease to control values by 6 h of withdrawal. In contrast, levels of RGS7 and -11 proteins, the only other subtypes for which antibodies are available, were not altered by these treatments. Intracellular application of wild-type RGS4, but not a GTPase accelerating-deficient mutant of RGS4, into LC neurons diminished electrophysiological responses to morphine. The observed subtype- and time-specific regulation of RGS4 protein and mRNA, and the diminished morphine-induced currents in the presence of elevated RGS4 protein levels, indicate that morphine induction of RGS4 could contribute to aspects of opiate tolerance and dependence displayed by LC neurons.
机译：本研究探讨了RGS（G蛋白信号的调节剂）蛋白在吗啡在蓝斑轨迹（LC）中的长期作用的可能作用，蓝斑是涉及鸦片物理依赖和戒断的脑干区域。吗啡通过微阿片受体的激活影响LC神经元，阿片受体与Gi / o相连，有望被RGS蛋白调节。我们专注于已知在该大脑区域表达的几种RGS亚型。慢性吗啡后，编码RGS2，-3，-4，-5，-7，-8和-11的mRNA的水平保持不变，但鸦片停药后6小时，RGS2和-4的mRNA水平升高了2-3倍。 。停药6小时后，RGS2和-4 mRNA的增加达到峰值，并在24小时后恢复到对照水平。 RGS4的免疫印迹分析显示，LC中mRNA和蛋白质反应之间存在显着差异：慢性吗啡后蛋白质水平升高了两倍，停药后6小时降低至对照值。相比之下，RGS7和-11蛋白（仅有的其他可获得抗体的亚型）的水平并未因这些处理而改变。细胞内应用野生型RGS4，而不是RGS4的GTPase加速缺陷型突变体，进入LC神经元可减少对吗啡的电生理反应。观察到的RGS4蛋白和mRNA的亚型和时间特异性调节，以及在RGS4蛋白水平升高的情况下吗啡诱导的电流降低，表明RGS4的吗啡诱导可能有助于鸦片类药物耐受性和LC神经元显示的依赖性。

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