Hooks Shelley B, Martemyanov Kirill, Zachariou Venetia
University of Georgia, Department of Pharmaceutical and Biomedical Sciences, Athens, GA, USA.
Biochem Pharmacol. 2008 Jan 1;75(1):76-84. doi: 10.1016/j.bcp.2007.07.045. Epub 2007 Aug 11.
The diverse family of Regulators of G protein signaling (RGS) proteins are widely distributed proteins with multiple functions, including GAP activity for heterotrimeric G protein alpha subunits. Three members of the RGS family, RGS9-2, RGS4 and RGSz, have been shown to play an essential modulatory role in psychostimulant and opiate drug actions. Interestingly, these proteins show distinct structure, distribution pattern and cellular localization. In addition, each of these proteins is differentially regulated by drugs of abuse in particular brain networks and appears to modulate distinct signal transduction events. The striatal enriched RGS9 plays a prominent role in opiate and psychostimulant drug reward; RGS4 appears to modulate opiate dependence via actions in the locus coeruleus, whereas RGSz modulates analgesia via activation of the PKC pathway.
G蛋白信号调节因子（RGS）蛋白家族种类多样，是广泛分布的多功能蛋白，包括对异源三聚体G蛋白α亚基的GAP活性。RGS家族的三个成员，即RGS9-2、RGS4和RGSz，已被证明在精神兴奋剂和阿片类药物作用中发挥重要的调节作用。有趣的是，这些蛋白具有不同的结构、分布模式和细胞定位。此外，这些蛋白中的每一种在特定脑网络中受到滥用药物的差异调节，并且似乎调节不同的信号转导事件。纹状体富集的RGS9在阿片类和精神兴奋剂药物奖赏中起重要作用；RGS4似乎通过在蓝斑核中的作用调节阿片类药物依赖性，而RGSz通过激活PKC途径调节镇痛。
