INSULIN POTENTIATES N-METHYL-D-ASPARTATE RECEPTOR ACTIVITY IN XENOPUS OOCYTES AND RAT HIPPOCAMPUS
INSULIN POTENTIATES N-METHYL-D-ASPARTATE RECEPTOR ACTIVITY IN XENOPUS OOCYTES AND RAT HIPPOCAMPUS
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DOI：
10.1016/0304-3940(95)11593-l
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发表时间：
1995-06-02
影响因子：
2.5
通讯作者：
MONAGHAN, DT
中科院分区：
文献类型：
--
作者：
LIU, LF;BROWN, JC;MONAGHAN, DT
生长因子信号转导通路最近被证明影响电压门控离子通道活性。在这项研究中，我们报道胰岛素可以调节配体门控离子通道的活性，即n -甲基- d-天冬氨酸（NMDA）受体。在非洲爪蟾卵母细胞中，短暂的胰岛素暴露可快速增强NR1a/NR2A和NR1a/NR2B受体反应2-3倍，并弱增强NR1a/NR2C和NR1a/NR2D介导的反应。staurosporine显著阻断了NR1a/NR2A受体的胰岛素增强反应，提示激酶参与了胰岛素作用。通过观察胰岛素增强海马切片中NMDA受体介导的突触成分，提示胰岛素对天然NMDA受体的调节。生长因子对NMDA受体活性的调节可能解释了生长因子对中枢神经系统兴奋性毒性的调节。
Growth factor signal transduction pathways have recently been shown to affect voltage-gated ion channel activity. In this study we report that insulin can modulate the activity of a ligand-gated ion channel, the N-methyl-D-aspartate (NMDA) receptor. In Xenopus oocytes, brief insulin exposure rapidly potentiated NR1a/NR2A and NR1a/NR2B receptor responses 2-3 fold and weakly potentiated NR1a/NR2C and NR1a/NR2D mediated-responses. Insulin potentiation of NR1a/NR2A receptor responses was significantly blocked by staurosporine, suggesting kinase involvement in insulin action. Insulin modulation of native NMDA receptors is suggested by the observation that insulin potentiated the NMDA receptor-mediated synaptic component in hippocampal slices. Regulation of NMDA receptor activity by growth factors may account for previous observations of growth factor modulation of central nervous system excitotoxicity.