Nash Family Department of Neuroscience, and Friedman Brain Institute (F.S., C.P., F.B., V.Z.) and Department of Pharmacological Sciences (V.Z.), Icahn School of Medicine at Mount Sinai, New York, New York.
Nash Family Department of Neuroscience, and Friedman Brain Institute (F.S., C.P., F.B., V.Z.) and Department of Pharmacological Sciences (V.Z.), Icahn School of Medicine at Mount Sinai, New York, New York
Mol Pharmacol. 2020 Dec;98(6):739-750. doi: 10.1124/mol.119.119206. Epub 2020 May 30.
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 G 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. SIGNIFICANCE STATEMENT: Regulator of G protein signaling (RGS) proteins are signal transduction modulators, expressed widely in various tissues, including brain regions mediating addiction and analgesia. Evidence from preclinical work suggests that members of the RGS family act by unique mechanisms in specific brain regions to control drug-induced plasticity. This review highlights interesting findings on the regulation and function of RGS proteins in models of analgesia and addiction.
RGS 蛋白（Regulator of G protein signaling）是一种多功能蛋白，在周围神经元细胞中表达，在发育、生理过程和药理反应中发挥关键作用。RGS 蛋白主要作为 G 蛋白偶联受体激活的 G 亚基的 GTPase 加速因子起作用，但它们也可以通过几种其他机制调节信号转导。在过去的二十年中，临床前工作确定了 RGS 家族的成员，它们在药物滥用的细胞内反应中具有独特且关键的作用。新的信息已经出现，表明 RGS 蛋白以脑区和激动剂选择性的方式调节阿片类镇痛药效力的机制。在成瘾和镇痛回路中，RGS 蛋白调节蛋白复合物和信号转导途径的机制也取得了进展。在这篇综述中，我们总结了 RGS 蛋白调节阿片类药物在镇痛和成瘾模型中功能反应的机制。我们还讨论了关于 RGS 蛋白在精神兴奋剂成瘾模型中的调节和功能的报告。利用过去 20 年进行的临床前研究的信息，我们强调了 RGS 蛋白复合物通过多种机制控制对阿片类药物和精神兴奋剂药物暴露的反应可塑性；我们进一步讨论了如何理解这些途径可能为 G 蛋白途径的治疗干预提供新的机会。
RGS 蛋白（Regulator of G protein signaling）是信号转导调节剂，广泛表达于各种组织中，包括参与成瘾和镇痛的脑区。临床前工作的证据表明，RGS 家族的成员在特定脑区通过独特的机制作用，以控制药物诱导的可塑性。这篇综述强调了 RGS 蛋白在镇痛和成瘾模型中的调节和功能的有趣发现。
