Phosphorylation of NR2B NMDA subunits by protein kinase C in arcuate nucleus contributes to inflammatory pain in rats
作者： Fan Bu , Huiyu Tian , Shan Gong , Qi Zhu , Guang-Yin Xu
DOI: 10.1038/SREP15945
关键词:
摘要: The arcuate nucleus (ARC) of the hypothalamus plays a key role in pain processing. Although it is well known that inhibition NMDA receptor (NMDAR) ARC attenuates hyperalgesia induced by peripheral inflammation, underlying mechanism NMDAR activation remains unclear. Protein kinase C (PKC) involved several signalling cascades activated physiological and pathological conditions. Therefore, we hypothesised upregulation PKC activates NMDARs ARC, thus contributing to inflammatory hyperalgesia. Intra-ARC injection chelerythrine (CC), specific inhibitor, attenuated complete Freund’s adjuvant (CFA) thermal mechanical dose-dependent manner. In vivo extracellular recordings showed microelectrophoresis CC or MK-801 (a antagonist) significantly reduced enhancement spontaneous discharges pain-evoked neurons. addition, CFA greatly enhanced expression total phosphorylated PKCγ ARC. Interestingly, also remarkably elevated level NR2B (Tyr1472) without affecting NR2B. Importantly, intra-ARC reversed subunits Taken together, inflammation leads an mediated producing
nature.com
harvard.edu
sci-hub.se 参考文章(55)
Jian-yu Lan, Vytenis A. Skeberdis, Teresa Jover, Sonja Y. Grooms, Ying Lin, Ricardo C. Araneda, Xin Zheng, Michael V. L. Bennett, R. Suzanne Zukin, Protein kinase C modulates NMDA receptor trafficking and gating. Nature Neuroscience. ,vol. 4, pp. 382- 390 ,(2001) , 10.1038/86028
WY Lu, ZG Xiong, S Lei, BA Orser, E Dudek, MD Browning, JF MacDonald, None, G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nature Neuroscience. ,vol. 2, pp. 331- 338 ,(1999) , 10.1038/7243
K. O. Aley, Robert O. Messing, Daria Mochly-Rosen, Jon D. Levine, Chronic Hypersensitivity For Inflammatory Nociceptor Sensitization Mediated by the ε Isozyme of Protein Kinase C The Journal of Neuroscience. ,vol. 20, pp. 4680- 4685 ,(2000) , 10.1523/JNEUROSCI.20-12-04680.2000
David R. Grosshans, Michael D. Browning, Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDA receptor. Journal of Neurochemistry. ,vol. 76, pp. 737- 744 ,(2008) , 10.1046/J.1471-4159.2001.00034.X
Andrei B. Petrenko, Tomohiro Yamakura, Hiroshi Baba, Koki Shimoji, The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review. Anesthesia & Analgesia. ,vol. 97, pp. 1108- 1116 ,(2003) , 10.1213/01.ANE.0000081061.12235.55
M. D. Dennis, C. S. Coleman, A. Berg, L. S. Jefferson, S. R. Kimball, REDD1 enhances protein phosphatase 2A–mediated dephosphorylation of Akt to repress mTORC1 signaling Science Signaling. ,vol. 7, ,(2014) , 10.1126/SCISIGNAL.2005103
Y.-J. Seo, M.-S. Kwon, S.-S. Choi, E.-J. Han, J.-S. Jung, H.-W. Choi, S.-H. Park, J.-E. Jang, H.-W. Suh, Characterization of the hypothalamic proopiomelanocortin gene and β-endorphin expression in the hypothalamic arcuate nucleus of mice elicited by inflammatory pain Neuroscience. ,vol. 152, pp. 1054- 1066 ,(2008) , 10.1016/J.NEUROSCIENCE.2007.06.047
Qiang Wang, Limin Mao, Jisheng Han, Characterization of inhibition of spinal nociceptive reflex by stimulation of the arcuate nucleus of the hypothalamus in the pentobarbital-anesthetized rat Pain. ,vol. 41, pp. 101- 108 ,(1990) , 10.1016/0304-3959(90)91114-X
Robert W. Gear, Christine Miaskowski, Newton C. Gordon, Steven M. Paul, Philip H. Heller, Jon D. Levine, The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain Pain. ,vol. 83, pp. 339- 345 ,(1999) , 10.1016/S0304-3959(99)00119-0
Yuan Zhang, Dongsheng Jiang, Junhong Zhang, Fen Wang, Xinghong Jiang, Jin Tao, Activation of neuromedin U type 1 receptor inhibits L-type Ca2+ channel currents via phosphatidylinositol 3-kinase-dependent protein kinase C epsilon pathway in mouse hippocampal neurons Cellular Signalling. ,vol. 22, pp. 1660- 1668 ,(2010) , 10.1016/J.CELLSIG.2010.06.006