Enhanced morphine analgesia in mice lacking β-arrestin 2
Enhanced morphine analgesia in mice lacking β-arrestin 2
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DOI：
10.1126/science.286.5449.2495
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发表时间：
1999-12-24
期刊：
影响因子：
56.9
通讯作者：
Lin, FT
中科院分区：
文献类型：
--
作者：
Bohn, LM;Lefkowitz, RJ;Lin, FT
吗啡的止痛作用是通过一种异三聚体鸟嘌呤核苷酸结合蛋白(G蛋白)偶联七螺旋受体(GPCRU阿片受体(MU OR)来实现的。受体与β-arrestin 1和β-arrestin 2的相互作用最终限制了受体的协同磷酸化。小鼠体内β-arrestin 2基因的功能缺失导致吗啡的镇痛作用显著增强和延长，提示MU或脱敏作用受到损害。这些结果提供了体内证据，证明了β-arrestin 2在调节特定gpr的功能方面的生理重要性。此外，他们提示，抑制β-arrestin 2功能可能导致吗啡的镇痛效果增强，并为研究和治疗疼痛、麻醉耐受和依赖提供潜在的新途径。
The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)-coupled heptahelical receptor (GPCR), the mu opioid receptor (mu OR). The efficiency of GPCR signaling is tightly regulated and ultimately Limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta-arrestin 1 and beta-arrestin 2. Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that mu OR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in regulating the function of a specific GPCR, the mu OR. Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence.