Vaccarino F M, Hayward M D, Nestler E J, Duman R S, Tallman J F
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
Brain Res Mol Brain Res. 1992 Jan;12(1-3):233-41. doi: 10.1016/0169-328x(92)90089-t.
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.
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。