R7BP Modulates Opiate Analgesia and Tolerance but not Withdrawal
R7BP Modulates Opiate Analgesia and Tolerance but not Withdrawal
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DOI：
10.1038/npp.2011.284
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发表时间：
2012-03-01
影响因子：
7.6
通讯作者：
Zachariou, Venetia
中科院分区：
文献类型：
--
作者：
Terzi, Dimitra;Cao, Yan;Zachariou, Venetia
适配蛋白R7家族结合蛋白（R7BP）通过调控G蛋白信号转导（RGS）蛋白的功能调控G蛋白偶联受体（GPCR）信号转导和脱敏。R7BP在整个大脑中表达，并似乎调节R7 RGS家族的三种蛋白的膜定位和稳定性：RGS6、RGS7和RGS9-2。RGS9-2是阿片和精神兴奋剂成瘾的有效负调节因子，促进吗啡镇痛耐受的发展，而RGS6和RGS7在成瘾中的作用尚不清楚。最近的研究表明，R7BP的功能性缺失通过阻止R7蛋白锚定在细胞膜上而降低了R7蛋白的活性，并增强了基底节区GPCR的反应性。在这里，我们利用R7BP敲除小鼠来研究R7蛋白在整个大脑中的功能干预如何影响阿片作用。我们的研究结果表明R7BP是吗啡镇痛和运动激活作用的负调节因子。我们还报道R7BP参与吗啡耐受性的发展。最后，我们的数据表明，尽管预防R7BP作用增强了对吗啡的镇痛反应，但它并不影响躯体戒断症状的严重程度。我们的数据表明，干预R7BP的作用可增强吗啡的镇痛效果，阻止耐受性，但不影响戒断，这表明R7BP复合物可能是镇痛药物的新靶点。神经精神药理学（2012）37,1005-1012；doi: 10.1038 / npp.2011.284;2011年11月16日在线发布
The adaptor protein R7 family binding protein (R7BP) modulates G protein coupled receptor (GPCR) signaling and desensitization by controlling the function of regulator of G protein signaling (RGS) proteins. R7BP is expressed throughout the brain and appears to modulate the membrane localization and stability of three proteins that belong to R7 RGS family: RGS6, RGS7, and RGS9-2. RGS9-2 is a potent negative modulator of opiate and psychostimulant addiction and promotes the development of analgesic tolerance to morphine, whereas the role of RGS6 and RGS7 in addiction remains unknown. Recent studies revealed that functional deletion of R7BP reduces R7 protein activity by preventing their anchoring to the cell membrane and enhances GPCR responsiveness in the basal ganglia. Here, we take advantage of R7BP knockout mice in order to examine the way interventions in R7 proteins function throughout the brain affect opiate actions. Our results suggest that R7BP is a negative modulator of the analgesic and locomotor activating actions of morphine. We also report that R7BP contributes to the development of morphine tolerance. Finally, our data suggest that although prevention of R7BP actions enhances the analgesic responses to morphine, it does not affect the severity of somatic withdrawal signs. Our data suggest that interventions in R7BP actions enhance the analgesic effect of morphine and prevent tolerance, without affecting withdrawal, pointing to R7BP complexes as potential new targets for analgesic drugs. Neuropsychopharmacology (2012) 37, 1005-1012; doi: 10.1038/npp.2011.284; published online 16 November 2011