Regulator of G protein signaling (RGS) proteins are multifunctional proteins expressed in peripheral and neuronal cells, playing critical roles in development, physiologic processes, and pharmacological responses. RGS proteins primarily act as GTPase accelerators for activated Gα subunits of G-protein coupled receptors, but they may also modulate signal transduction by several other mechanisms. Over the last two decades, preclinical work identified members of the RGS family with unique and critical roles in intracellular responses to drugs of abuse. New information has emerged on the mechanisms by which RGS proteins modulate the efficacy of opioid analgesics in a brain region– and agonist-selective fashion. There has also been progress in the understanding of the protein complexes and signal transduction pathways regulated by RGS proteins in addiction and analgesia circuits. In this review, we summarize findings on the mechanisms by which RGS proteins modulate functional responses to opioids in models of analgesia and addiction. We also discuss reports on the regulation and function of RGS proteins in models of psychostimulant addiction. Using information from preclinical studies performed over the last 20 years, we highlight the diverse mechanisms by which RGS protein complexes control plasticity in response to opioid and psychostimulant drug exposure; we further discuss how the understanding of these pathways may lead to new opportunities for therapeutic interventions in G protein pathways.

中文翻译：

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镇痛和成瘾中 G 蛋白信号传导的调节剂。

G 蛋白信号调节剂 (RGS) 蛋白是在外周细胞和神经元细胞中表达的多功能蛋白，在发育、生理过程和药理反应中起着关键作用。RGS 蛋白主要作为激活 G α 的GTPase 加速器G 蛋白偶联受体的亚基，但它们也可能通过其他几种机制调节信号转导。在过去的二十年里，临床前工作确定了 RGS 家族的成员在对滥用药物的细胞内反应中具有独特而关键的作用。关于 RGS 蛋白在大脑区域和激动剂选择性方式中调节阿片类镇痛药功效的机制的新信息已经出现。在对成瘾和镇痛回路中由 RGS 蛋白调节的蛋白质复合物和信号转导通路的理解方面也取得了进展。在这篇综述中，我们总结了关于 RGS 蛋白在镇痛和成瘾模型中调节对阿片类药物的功能反应的机制的发现。我们还讨论了关于精神兴奋剂成瘾模型中 RGS 蛋白的调节和功能的报告。使用来自过去 20 年临床前研究的信息，我们强调了 RGS 蛋白复合物控制可塑性以响应阿片类药物和精神兴奋剂药物暴露的多种机制；我们进一步讨论了对这些通路的理解如何为 G 蛋白通路的治疗干预带来新的机会。