Src-dependent phosphorylation of mu-opioid receptor at Tyr(336) modulates opiate withdrawal
文献类型：期刊论文
| 作者 | Zhang, Lei2; Kibaly, Cherkaouia2; Wang, Yu-Jun1,3 ; Xu, Chi2; Song, Kyu Young2; McGarrah, Patrick W.2; Loh, Horace H.2; Liu, Jing-Gen1,3; Law, Ping-Yee2
|
| 刊名 | EMBO MOLECULAR MEDICINE
 |
| 出版日期 | 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. |
| WOS关键词 | ADENYLYL-CYCLASE SUPERACTIVATION ; MOLECULAR-MECHANISMS ; MORPHINE-WITHDRAWAL ; NUCLEUS-ACCUMBENS ; PROTEIN-KINASE ; SIGNALING PATHWAY ; COCAINE ADDICTION ; FAMILY KINASES ; FYN-KINASE ; REWARD |
| 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研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000414339700006 |
| 出版者 | WILEY |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。