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学科主题基础医学
Disruption of delta-opioid receptor phosphorylation at Threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity
Chen, Hai-Jing1; Xie, Wei-Yan2; Hu, Fang1; Zhang, Ying1; Wang, Jun3; Wang, Yun1
关键词inflammatory hypersensitivity cyclin-dependent kinase 5 delta-opioid receptor morphine tolerance
刊名NEUROSCIENCE BULLETIN
2012-04-01
DOI10.1007/s12264-012-1216-8
28期:2页:182-192
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for Doctoral Program of Higher Education Grants, China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for Doctoral Program of Higher Education Grants, China
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]DORSAL-ROOT GANGLIA ; OPIATE RECEPTORS ; ANTINOCICEPTIVE TOLERANCE ; INTESTINAL INFLAMMATION ; TRIGEMINAL NOCICEPTORS ; FUNCTIONAL COMPETENCE ; KNOCKOUT MICE ; MU ; PAIN ; ANALGESIA
英文摘要

Objective Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the delta-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund′s adjuvant (CFA)-induced inflammatory pain and morphine tolerance. Methods Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain. Results Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not mu-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain. Conclusion Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.

语种英语
所属项目编号30830044 ; 30925015 ; 30800330 ; 81161120497 ; 7092061 ; 200800011028 ; 20060001121
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for Doctoral Program of Higher Education Grants, China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for Doctoral Program of Higher Education Grants, China
WOS记录号WOS:000304463800011
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被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67780
专题北京大学基础医学院_神经生物学系
作者单位1.Peking Univ, Neurosci Res Inst, Dept Neurobiol, Sch Basic Med Sci, Beijing 100191, Peoples R China
2.Capital Med Univ, Beijing Tiantan Hosp, Beijing Neurosurg Inst, Beijing 100050, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Dept Anat & Histol, Beijing 100191, Peoples R China
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Chen, Hai-Jing,Xie, Wei-Yan,Hu, Fang,et al. Disruption of delta-opioid receptor phosphorylation at Threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity[J]. NEUROSCIENCE BULLETIN,2012,28(2):182-192.
APA Chen, Hai-Jing,Xie, Wei-Yan,Hu, Fang,Zhang, Ying,Wang, Jun,&Wang, Yun.(2012).Disruption of delta-opioid receptor phosphorylation at Threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.NEUROSCIENCE BULLETIN,28(2),182-192.
MLA Chen, Hai-Jing,et al."Disruption of delta-opioid receptor phosphorylation at Threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity".NEUROSCIENCE BULLETIN 28.2(2012):182-192.
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