A new splice of life for the μ-opioid receptor.
A new splice of life for the μ-opioid receptor.
复制标题
γ-阿片受体的新生命拼接。
DOI：
10.1172/jci82060
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Mannes,AndrewJ
中科院分区：
文献类型：
--
作者：
Iadarola,MichaelJ;Sapio,MatthewR;Mannes,AndrewJ
μ-Opioid agonists mediate their analgesic effect through GPCRs that are generated via alternate splicing of theOprm1transcript. While the majority of μ-opioids interact with receptors comprising the canonical 7 transmembrane (7TM) domain, a recently identified class of μ-opioids appears to require a 6TM domain variant. In this issue of theJCI, Lu and colleagues provide an in vivo proof-of-concept demonstration that a 6TM isoform of the μ-opioid receptor can support functional analgesia inOprm1-deficent animals. The 6TM isoform was pharmacologically distinct from the canonical 7TM μ-opioid receptor, and 6TM agonists had a reduced side effect profile, which confers a strong therapeutic advantage over standard opioid analgesics. The observations of Lu et al. extend the reach of opioid-receptor neurobiology and pharmacology into a new era of analgesic discovery. This advance emerges from a series of fundamental research analyses in which elements of the endogenous opioid system were frequently in the vanguard.
