Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation.
Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation.
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DOI：
10.1186/1744-8069-1-25
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发表时间：
2005-09-02
期刊：
影响因子：
3.3
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
--
作者：
Caudle RM;Perez FM;Del Valle-Pinero AY;Iadarola MJ
脊髓n -甲基- d -天冬氨酸（NMDA）受体密切参与中枢致敏的发展和维持。然而，介导NMDA受体功能改变的机制尚不清楚。在这项研究中，研究了NR1剪接变异体和NR2亚基在大鼠后爪炎症后磷酸化的作用。我们进一步检测了这些蛋白在损伤后的表达水平。发现在卡拉胶诱导后爪炎症2小时内，腰椎脊髓NR1亚基在丝氨酸残基上被磷酸化。增强的NR1丝氨酸磷酸化在6小时内逆转。未观察到NR1苏氨酸或酪氨酸残基的磷酸化。同样，在丝氨酸、苏氨酸和酪氨酸残基上也没有观察到NR2亚基磷酸化。对NR1和NR2蛋白表达的分析表明，炎症后NR1剪接变异体或NR2A的水平没有变化。然而，脊髓NR2B的表达受到后爪炎症的抑制。NR2B的表达在炎症开始后的一个多星期内一直处于抑制状态。这些数据表明NR1丝氨酸磷酸化导致脊髓外周损伤后NMDA受体活性的初始增加。NR2B表达的抑制提示了对伤害性活动增强的补偿。这些数据表明，脊髓NMDA受体在损伤后中枢致敏的发育、维持和恢复过程中是高度动态的。因此，针对NMDA受体的慢性疼痛治疗应该针对NMDA受体亚基的确切结构和疾病特定阶段存在的翻译后修饰进行设计。
Spinal cord N-methyl-D-aspartate (NMDA) receptors are intimately involved in the development and maintenance of central sensitization. However, the mechanisms mediating the altered function of the NMDA receptors are not well understood. In this study the role of phosphorylation of NR1 splice variants and NR2 subunits was examined following hind paw inflammation in rats. We further examined the level of expression of these proteins following the injury. Lumbar spinal cord NR1 subunits were found to be phosphorylated on serine residues within two hours of the induction of hind paw inflammation with carrageenan. The enhanced NR1 serine phosphorylation reversed within six hours. No phosphorylation on NR1 threonine or tyrosine residues was observed. Likewise, no NR2 subunit phosphorylation was observed on serine, threonine or tyrosine residues. An analysis of NR1 and NR2 protein expression demonstrated no change in the levels of NR1 splice variants or NR2A following the inflammation. However, spinal cord NR2B expression was depressed by the hind paw inflammation. The expression of NR2B remained depressed for more than one week following initiation of the inflammation. These data suggest that NR1 serine phosphorylation leads to an initial increase in NMDA receptor activity in the spinal cord following peripheral injury. The suppression of NR2B expression suggests compensation for the enhanced nociceptive activity. These data indicate that spinal cord NMDA receptors are highly dynamic in the development, maintenance and recovery from central sensitization following an injury. Thus, chronic pain therapies targeted to NMDA receptors should be designed for the exact configuration of NMDA receptor subunits and post-translational modifications present during specific stages of the disease.
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影响因子：
2.5
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