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皮质和纹状体神经元原代培养物中兴奋性氨基酸受体类型对即刻早期基因的差异诱导

Differential induction of immediate early genes by excitatory amino acid receptor types in primary cultures of cortical and striatal neurons.

作者信息

Vaccarino F M, Hayward M D, Nestler E J, Duman R S, Tallman J F

机构信息

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.

出版信息

Brain Res Mol Brain Res. 1992 Jan;12(1-3):233-41. doi: 10.1016/0169-328x(92)90089-t.

Abstract

In primary cultures of neurons from cerebral cortex and striatum, 30 s stimulation with the excitatory amino acid glutamate elicited a 5 to 9-fold increase in immediate early gene (IEG) mRNAs. Glutamate increased c-fos, c-jun, jun-B, and NGFI-A (zif/268) mRNAs by binding to both alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor types, and increased c-fos, jun-B, and NGFI-A mRNAs by binding to the metabotropic receptor. NMDA receptor activation elicited IEG expression by a transmembrane calcium influx; AMPA receptor-induced depolarization played a permissive role for the opening of the NMDA receptor channel. The protein kinase C (PKC) inhibitor H-7 (but not inhibitors of cyclic nucleotide-dependent and calcium/calmodulin-dependent protein kinases) partially blocked IEG expression induced by glutamate.

摘要

在来自大脑皮层和纹状体的神经元原代培养物中,用兴奋性氨基酸谷氨酸进行30秒刺激可使即刻早期基因(IEG)mRNA增加5至9倍。谷氨酸通过与α-氨基-3-羟基-5-甲基异恶唑丙酸(AMPA)和N-甲基-D-天冬氨酸(NMDA)受体类型结合,增加c-fos、c-jun、jun-B和NGFI-A(zif/268)mRNA,并通过与促代谢型受体结合增加c-fos、jun-B和NGFI-A mRNA。NMDA受体激活通过跨膜钙内流引发IEG表达;AMPA受体诱导的去极化对NMDA受体通道的开放起允许作用。蛋白激酶C(PKC)抑制剂H-7(而非环核苷酸依赖性和钙/钙调蛋白依赖性蛋白激酶抑制剂)部分阻断了谷氨酸诱导的IEG表达。

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