Induction of primary response genes by excitatory amino acid receptor agonists in primary astroglial cultures

Daniele F. Condorelli, Paola Dell'Albani, Carla Amico, Leszek Kaczmarek, Ferdinande Nicoletti, Katarzyna Lukasiuk, Anna Maria Giuffrida Stella

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Abstract

We have characterized the genomic response of astroglial cells to excitatory amino acids by using selective agonists and antagonists for the various receptor subtypes and by analyzing different primary response genes, such as members of the Fos (c-fos and fosB) and Jun (c-jun, junB, and jun D) families, zif/268, and c-myc. A rapid and transient elevation of mRNA levels for c-fos, fosB, c-jun, junB, and zif/268 was observed after addition of glutamate to cultured astrocytes, whereas junD and c-myc expression was not affected. The level of AP-1 DNA binding activity, as measured by the electrophoretic mobility shift assay, also increased after addition of glutamate to cultured astrocytes. Glutamate-induced c-fos expression was not affected by the N-methyl-D-aspartate receptor antagonists MK-801 and D-2-amino-5-phosphonopentanoate, by the kainate/α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist 6,7-dinitroquinoxaline-2,3- dione (DNQX), or by the broad-spectrum antagonist kynurenate. Kainate and AMPA were also effective in inducing primary response gene expression, and their actions were antagonized by kynurenate and DNQX but not by MK-801. 1S,3R-1-Aminocyclopentane-1,3-dicarboxylic acid, a selective agonist for the metabotropic glutamate receptor, induced primary response gene expression, but its action was not antagonized by different glutamate antagonists, including L-2-amino-3-phosphonopropionate. In conclusion, our data suggest that cultured astrocytes express both kainate/AMPA ionotropic receptors and metabotropic receptors coupled to the rapid and coordinated activation of different classes of transcriptional factor genes.

Original languageEnglish
Pages (from-to)877-885
Number of pages9
JournalJournal of Neurochemistry
Volume60
Issue number3
Publication statusPublished - 1993

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Keywords

  • Astroglia
  • Excitatory amino acids
  • Primary response genes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Condorelli, D. F., Dell'Albani, P., Amico, C., Kaczmarek, L., Nicoletti, F., Lukasiuk, K., & Stella, A. M. G. (1993). Induction of primary response genes by excitatory amino acid receptor agonists in primary astroglial cultures. Journal of Neurochemistry, 60(3), 877-885.