Arcuate Src activation-induced phosphorylation of NR2B NMDA subunit contributes to inflammatory pain in rats
Arcuate Src activation-induced phosphorylation of NR2B NMDA subunit contributes to inflammatory pain in rats
复制标题
弓形 Src 激活诱导的 NR2B NMDA 亚基磷酸化导致大鼠炎症性疼痛
DOI：
10.1152/jn.01047.2011
复制
发表时间：
2012-12-01
影响因子：
2.5
通讯作者：
Jiang, Xinghong
中科院分区：
文献类型：
--
作者：
Xu, Longsheng;Pan, Yanyan;Jiang, Xinghong
徐亮，潘毅，朱强，龚胜，陶杰，徐戈伊，蒋晓. Arcuate Src激活诱导的NR 2B NMDA亚基磷酸化参与大鼠炎性疼痛J Neurophysiol 108：3024-3033，2012.首次发表于2012年9月9日; doi：10.1152/jn.01047.2011.- Src家族酪氨酸激酶在外周炎症后的中枢致敏中起重要作用。然而，是否Src家族在弓状核（ARC）的下丘脑内侧基底核参与中枢敏化仍然是未知的。本研究旨在探讨Src家族酪氨酸激酶在外周炎症后ARC N-甲基-D-天冬氨酸（NMDA）受体活性变化中的作用及其机制。通过将完全弗氏佐剂（CFA）单侧注射到大鼠后爪中诱导外周炎症。采用电生理场记录法记录对照组和CFA大鼠下丘脑中基底节脑片ARC的神经元活动。Western blot和免疫沉淀法分析总Src和NR 2B亚基蛋白的表达和磷酸化Src和NR 2B亚基蛋白的表达。我们的研究结果表明，CFA注射导致机械和热敏感性的增加，这是部分阻断新生儿谷氨酸治疗。CFA注射还增强了ARC神经元的自发放电，这被NMDA受体NR 2B亚单位特异性拮抗剂Ro 25 -6981和Src家族酪氨酸激酶抑制剂PP 2逆转。此外，外周炎症增强Src磷酸化和NMDA受体NR 2B亚基磷酸化，而不改变ARC中总NR 2B亚基的表达。外周炎症也增加了ARC中NR 2B蛋白与p-Src蛋白的关联。PP 2的施用阻断了CFA注射诱导的NR 2B磷酸化的上调。综上所述，我们目前的研究结果表明，弓状Src激活诱导的NR 2B NMDA亚基的酪氨酸磷酸化可能有助于炎症性疼痛。
Xu L, Pan Y, Zhu Q, Gong S, Tao J, Xu GY, Jiang X. Arcuate Src activation-induced phosphorylation of NR2B NMDA subunit contributes to inflammatory pain in rats. J Neurophysiol 108: 3024-3033, 2012. First published September 9, 2012; doi: 10.1152/jn.01047.2011.-The tyrosine kinases of Src family play an important role in the central sensitization following peripheral inflammation. However, whether the Src family in the arcuate nucleus (ARC) of mediobasal hypothalamus is involved in central sensitization remains unknown. The aim of this study was to investigate the role and mechanisms of tyrosine kinases of Src family in N-methyl-D-aspartate (NMDA) receptor activity in the ARC following peripheral inflammation. Peripheral inflammation was induced by unilateral injection of complete Freund's adjuvant (CFA) into rat hindpaw. The neuronal activities of the ARC were recorded using electrophysiological field recording from the in vitro mediobasal hypothalamic slices from control and CFA rats. Expression of total and phosphorylated Src and NR2B subunit protein was analyzed by Western blot and immuoprecipitation. Our results showed that CFA injection resulted in an increase in mechanical and thermal sensitivity, which was partially blocked by neonatal monosodium glutamate treatment. CFA injection also enhanced spontaneous firings of ARC neurons, which were reversed by the NMDA receptor NR2B subunit specific antagonist Ro25-6981 and by PP2, an Src family tyrosine kinase inhibitor. In addition, peripheral inflammation enhanced Src phosphorylation and NMDA receptor NR2B subunit phosphorylation without alteration of total NR2B subunit expression in the ARC. Peripheral inflammation also increased the association of NR2B protein with p-Src protein in the ARC. Administration of PP2 blocked the upregulation of NR2B phosphorylation induced by CFA injection. Taken together, our present results suggest that the arcuate Src activation-induced tyrosine phosphorylation of NR2B NMDA subunit may contribute to inflammatory pain.