N-methyl-D-aspartate antagonists block fos-like protein expression induced via multiple signaling pathways in cultured cortical neurons

Kinya Hisanaga, Stephen M. Sagar, Frank R Sharp

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

c-fos mRNA and Fos-like protein(s) (FLP) are induced in cultured cortical neurons by glutamate, high K+, phorbol ester, basic fibroblast growth factor, Zn2+, and vasoactive intestinal peptide. Glutamate induction of c-fos mRNA and FLP is blocked by noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and competitive NMDA antagonists, 4-(3-phosphonopropyl)piperazin-2-carboxylic acid and 2-amino-7-phosphonoheptanoate. These antagonists partially block high K+-, phorbol ester-, Zn2+-, and VIP-induced c-fos mRNA expression, but have no effect on bFGF-induced c-fos mRNA expression. However, both competitive and noncompetitive NMDA antagonists completely block FLP induction by all of these agents without affecting total protein synthesis. Therefore, these NMDA antagonists block FLP translation, without blocking c-fos transcription. It is hypothesized that NMDA receptor activation is required for translation of c-fos mRNA in cortical neurons after stimulation of multiple intracellular signaling pathways. It is possible that NMDA antagonists prevent cortical plasticity by blocking induction of the Fos protein that would normally be induced by neurotrophic factors, neurotransmitters, and neuromodulators.

Original languageEnglish (US)
Pages (from-to)1836-1844
Number of pages9
JournalJournal of Neurochemistry
Volume58
Issue number5
StatePublished - May 1992
Externally publishedYes

Keywords

  • c-fos
  • Fibroblast growth factor
  • N-Methyl-D-aspartate receptor
  • Translational regulation
  • Vasoactive intestinal peptide
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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