Fang Li, Wu Jing, Lin Qing, Willis William D
Division of Neurosurgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Brain Res Mol Brain Res. 2003 Oct 21;118(1-2):160-5. doi: 10.1016/j.molbrainres.2003.08.002.
The present project was designed to investigate the role of protein kinase A (PKA) and protein kinase C (PKC) in the regulation of phosphorylation of the GluR1 subunits of AMPA receptors in the spinal cord of rats after capsaicin injection. We found that after capsaicin injection, a significant upregulation of phosphorylated GluR1 both at Ser(831) and Ser(845) was detected on the side ipsilateral to the injection. Intrathecal treatment with a PKA inhibitor, H89 ([N-[2-((3-bromophenyl)-2-propenyl)amino)ethyl]-5-isoquinoline sulfonamide, HCl), or a PKC inhibitor, NPC15473 (2,6-diamino-N-([1-oxotridecyl)-2-piperidinyl]methyl)hexanamide), significantly blocked the increased phosphorylation at different serine sites without affecting the GluR1 protein itself. Our results suggest that increased phosphorylation of the GluR1 subunit of AMPA receptors contributes to central sensitization following acute peripheral inflammation, and the effect may occur at different phosphorylation sites through the activation of the PKA or PKC protein kinase cascades.
本项目旨在研究蛋白激酶A（PKA）和蛋白激酶C（PKC）在辣椒素注射后大鼠脊髓中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体GluR1亚基磷酸化调节中的作用。我们发现，辣椒素注射后，在注射同侧检测到Ser（831）和Ser（845）位点磷酸化的GluR1显著上调。鞘内注射PKA抑制剂H89（[N-[2-((3-溴苯基)-2-丙烯基)氨基)乙基]-5-异喹啉磺酰胺，盐酸盐）或PKC抑制剂NPC15473（2,6-二氨基-N-([1-氧代十三烷基)-2-哌啶基]甲基)己酰胺），可显著阻断不同丝氨酸位点磷酸化的增加，而不影响GluR1蛋白本身。我们的结果表明，AMPA受体GluR1亚基磷酸化增加有助于急性外周炎症后的中枢敏化，且该效应可能通过PKA或PKC蛋白激酶级联反应的激活在不同磷酸化位点发生。
