Induction of immediate early genes by cyclic AMP in primary cultures of neurons from rat cerebral cortex.
In this paper, we tested whether physiological activators of the cAMP second messenger pathway in primary cultures of neurons from rat cerebral cortex directly induce c-fos and other immediate early gene (IEG) transcription factors. We have found that brief (30 s to 2 min) stimulation of neurons with vasoactive intestinal peptide (VIP) and SKF-38393, a D1-dopaminergic receptor agonist, potently increased mRNA levels for the IEGs c-fos, jun-B, and NGFI-A, with weaker increases for c-jun. This action was mimicked by forskolin and dibutyryl cAMP. IEG induction by VIP and dibutyryl cAMP was not blocked by excitatory amino acid receptor antagonists or by blockers of dihydropyridine-sensitive calcium channels. Moreover, calcium-free medium did not modify IEG induction by dibutyryl cAMP, suggesting that cAMP can directly regulate IEG expression in differentiated neurons independently of calcium.
Vaccarino
F M
FM
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
Hayward
M D
MD
Le
H N
HN
Hartigan
D J
DJ
Duman
R S
RS
Nestler
E J
EJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015259:Dopamine Agents / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D004873:Ergolines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016762:Genes, fos; D016758:Genes, jun; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D007700:Kinetics; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D015290:Second Messenger Systems; D014157:Transcription Factors / Q000096:biosynthesis*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D004268:DNA-Binding Proteins; D015259:Dopamine Agents; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004873:Ergolines; D005971:Glutamates; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D005576:Colforsin; D019257:Quinpirole; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D003994:Bucladesine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP