β-arrestin与吗啡耐受性

β-arrestin and morphine tolerance

吗啡耐受的形成可归因于受体的脱敏、内化和受体下游信号的调控。许多研究表明β-arrestin在阿片受体的脱敏、内化和吗啡耐受形成过程中起关键作用。敲除小鼠控制阿片受体内化的蛋白β-arrestin2基因后。吗啡的镇痛作用明显增强而耐受减弱。最近研究还发现8阿片受体(DOR)的激动可以导致β-arrestin1向核内转移,同时促进依赖β-arrestin1的p27和c-fos的转录,表明β-arrestin具有将受体信号传人细胞核内的信使作用。本综述简要概括了近年来关于β-arrestin与吗啡耐受的研究进展。

Receptor desensitization and intemalization and post - receptor regulation could be attributed to the development of opioid tolerance. Many studies have suggested a key role of β-arrestin in the de-sensitization, internalization of opioid receptors and opioid tolerance. Deletion of the β-arrestin2 gene in mice resulted in enhanced analgesic effects and reduced tolerance after morphine administration. Recent studies have shown that activation of DOR could induce β-arrestin 1 translocation to the nucleus and stimulate β-arrestin - dependent p27 and c - fos transcription, thus revealing a novel function of 13-arrestin as a messenger carrying receptor signals to the nucleus. In this review,we discuss the recent findings on β-arrestins and their roles in the development of morphine tolerance.