Differential activation of protein kinases in the dorsal horn in vitro of normal and inflamed rats by group I metabotropic glutamate receptor subtypes
Differential activation of protein kinases in the dorsal horn in vitro of normal and inflamed rats by group I metabotropic glutamate receptor subtypes
复制标题
DOI：
10.1016/j.neuropharm.2007.04.003
复制
发表时间：
2007-07-01
影响因子：
4.7
通讯作者：
King, A. E.
中科院分区：
文献类型：
--
作者：
Giles, P. A.;Trezise, D. J.;King, A. E.
I 类代谢型谷氨酸受体 (mGluR) 有助于脊髓敏化和突触可塑性，但其潜在机制尚不清楚。在这里，在幼年大鼠中研究了 I 组 mGluR 对体外凝胶质 (SG) 神经元诱发的单突触兴奋性突触后电流 (EPSC) 的调节。此外，在河豚毒素（TTX）处理的幼稚大鼠和患有完全弗氏佐剂（CIA）外周炎症的大鼠的体外脊髓中确定了I组mGluRs在背角神经元Fos表达中的作用。在大多数 SG 神经元中，(S)-3,5-二羟基苯基甘氨酸 (DHPG) 减少 EPSC，并且这种作用被 mGluR(5) 拮抗剂 2-甲基 - 6-(苯乙炔基)-吡啶 (MPEP) 抑制。配对脉冲和自发微型兴奋性突触后电流 (mEPSC) 的数据表明，mGluR5 在突触前发挥作用，减少递质释放。 DHPG 诱导的 EPSC 振幅降低是通过 PKC（而非 ERK）信号级联起作用的。在初始小鼠而非 CFA 大鼠的背角中，DHPG 增加了 Fos 的表达，而 MPEP 以及 PKC 和 ERK 抑制剂则降低了 Fos 的表达。在 CFA 组中，MPEP 和激酶抑制剂降低了基础 Fos 表达。这些数据推断 mGluR(5) 在背角内伤害性突触功效的急性调节和转录因子（例如与活动依赖性神经可塑性适应有关的 Fos）突触后激活中的作用。这些作用是通过 PKC 和 ERK 依赖性转导途径的差异激活来实现的。 (c) 2007 Elsevier Ltd. 保留所有权利。
Group I metabotropic glutamate receptors (mGluRs) contribute to spinal sensitization and synaptic plasticity but the underlying mechanisms are unknown. Here, group I mGluR modulation of evoked monosynaptic excitatory postsynaptic currents (EPSCs) in substantia gelatinosa (SG) neurones in vitro was investigated in juvenile rats. In addition, the role of group I mGluRs in dorsal horn neuronal Fos expression was determined in tetrodotoxin (TTX)-treated in vitro spinal cords of naive rats and those with Complete Freund's Adjuvant (CIA) peripheral inflammation. In the majority of SG neurones, (S)-3,5-Dihydroxyphenylglycine (DHPG) reduced EPSCs and this effect was inhibited by the mGluR(5) antagonist 2-Methyl - 6-(phenylethynyl)-pyridine (MPEP). Data for paired-pulse and spontaneous miniature excitatory postsynaptic currents (mEPSCs) suggest mGluR5 acts presynaptically to reduce transmitter release. DHPG-induced reduction of EPSC amplitude operated via PKC, but not ERK, signalling cascade. In the dorsal horn of naive but not CFA rats, DHPG increased Fos expression and this was reduced by MPEP and both PKC and ERK inhibitors. In the CFA group, basal Fos expression was reduced by MPEP and the kinase inhibitors. These data infer a role for mGluR(5) in acute modulation of nociceptive synaptic efficacy within the dorsal horn and postsynaptic activation of transcription factors such as Fos that are implicated in activity-dependent neuroplastic adaptation. These actions are achieved by differential activation of PKC- and ERK-dependent transduction pathways. (c) 2007 Elsevier Ltd. All rights reserved.