Src-dependent phosphorylation of mu-opioid receptor at Tyr(336) modulates opiate withdrawal

doi:10.15252/emmm.201607324

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	Src-dependent phosphorylation of mu-opioid receptor at Tyr(336) modulates opiate withdrawal
	Zhang, Lei 2; Kibaly, Cherkaouia 2; Wang, Yu-Jun1,3 ; Xu, Chi 2; Song, Kyu Young 2; McGarrah, Patrick W.2; Loh, Horace H.2; Liu, Jing-Gen1,3 ; Law, Ping-Yee 2
刊名	EMBO MOLECULAR MEDICINE
	2017-11
卷号	9 期号:11 页码:1521-1536
关键词	lentivirus injection locus coeruleus naloxone-precipitated opiate withdrawal opiate addiction Src-mediated phosphorylation of MOR at Tyr(336)
ISSN号	1757-4676
DOI	10.15252/emmm.201607324
文献子类	Article
英文摘要	Opiate withdrawal/negative reinforcement has been implicated as one of the mechanisms for the progression from impulsive to compulsive drug use. Increase in the intracellular cAMP level and protein kinase A (PKA) activities within the neurocircuitry of addiction has been a leading hypothesis for opiate addiction. This increase requires the phosphorylation of mu-opioid receptor (MOR) at Tyr(336) by Src after prolonged opiate treatment invitro. Here, we report that the Src-mediated MOR phosphorylation at Tyr(336) is a prerequisite for opiate withdrawal in mice. We observed the recruitment of Src in the vicinity of MOR and an increase in phosphorylated Tyr(336) (pY336) levels during naloxone-precipitated withdrawal. The intracerebroventricular or stereotaxic injection of a Src inhibitor (AZD0530), or Src shRNA viruses attenuated pY336 levels, and several somatic withdrawal signs. This was also observed in Fyn(-/-) mice. The stereotaxic injection of wild-type MOR, but not mutant (Y336F) MOR, lentiviruses into the locus coeruleus of MOR-/- mice restored somatic withdrawal jumping. Regulating pY336 levels during withdrawal might be a future target for drug development to prevent opiate addictive behaviors.
资助项目	National Institutes of Health, USA[DA031442] ; Ministry of Science and Technology of China[2013CB835100] ; Ministry of Science and Technology of China[2015CB553502] ; National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[81671322] ; National Natural Science Foundation of China[81401107] ; Chinese Academy of Sciences[2011T2529] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017334]
WOS关键词	ADENYLYL-CYCLASE SUPERACTIVATION ; MOLECULAR-MECHANISMS ; MORPHINE-WITHDRAWAL ; NUCLEUS-ACCUMBENS ; PROTEIN-KINASE ; SIGNALING PATHWAY ; COCAINE ADDICTION ; FAMILY KINASES ; FYN-KINASE ; REWARD
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	WILEY
WOS记录号	WOS:000414339700006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272429]
专题	药理学第二研究室
通讯作者	Kibaly, Cherkaouia; Liu, Jing-Gen; Law, Ping-Yee
作者单位	1.Chinese Acad Sci, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China 2.Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Zhang, Lei,Kibaly, Cherkaouia,Wang, Yu-Jun,et al. Src-dependent phosphorylation of mu-opioid receptor at Tyr(336) modulates opiate withdrawal[J]. EMBO MOLECULAR MEDICINE,2017,9(11):1521-1536.
APA	Zhang, Lei.,Kibaly, Cherkaouia.,Wang, Yu-Jun.,Xu, Chi.,Song, Kyu Young.,...&Law, Ping-Yee.(2017).Src-dependent phosphorylation of mu-opioid receptor at Tyr(336) modulates opiate withdrawal.EMBO MOLECULAR MEDICINE,9(11),1521-1536.
MLA	Zhang, Lei,et al."Src-dependent phosphorylation of mu-opioid receptor at Tyr(336) modulates opiate withdrawal".EMBO MOLECULAR MEDICINE 9.11(2017):1521-1536.