Differential induction of immediate early genes by excitatory amino acid receptor types in primary cultures of cortical and striatal neurons.
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.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
F M
FM
Vaccarino
M D
MD
Hayward
E J
EJ
Nestler
R S
RS
Duman
J F
JF
Tallman
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology*; D017874:Immediate-Early Proteins; D007546:Isoquinolines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011519:Proto-Oncogenes / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D005971:Glutamates; D017874:Immediate-Early Proteins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D013449:Sulfonamides; D014157:Transcription Factors; D018698:Glutamic Acid; C017967:W 7; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016318:Quisqualic Acid; D005998:Glycine