In primary cultures of cerebellar granule cells the activation of N-methyl-D-aspartate-sensitive glutamate receptors induces c-fos mRNA expression.
L-Glutamate, the natural agonist of quisqualate- and N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid receptors, elicits a rapid, transient, dose-dependent increase of the steady state level of c-fos mRNA followed by an accumulation of c-fos protein immunostaining in cell nuclei. This induction is prevented by 2-amino-5-phosphonovalerate, an isosteric glutamate receptor antagonist, and by Mg2+ ion and phencyclidine, two noncompetitive allosteric antagonists of NMDA-sensitive glutamate receptors. Kainate and quisqualate (up to 150 microM) failed to alter the basal expression of c-fos mRNA. Furthermore, glycine, a positive allosteric modulator of NMDA-sensitive glutamate receptors, potentiated the glutamate response in a strychnine-insensitive manner. Activation of other transmitter receptors present in these cells (gamma-aminobutyric acid(A), gamma-aminobutyric acid(B), and muscarinic) failed to increase c-fos mRNA expression. Our results provide evidence that activation of NMDA-sensitive glutamate receptors plays an exclusive role in the induction of c-fos mRNA expression and translation in primary cultures of granule cells. It can be inferred that, by this mechanism, glutamate can initiate a transcriptional program that may result in changes in the simultaneous expression of a set of target genes involved in neuron-specific responses.
Szekely
A M
AM
FIDIA-Georgetown Institute for the Neurosciences, Georgetown University, Washington, DC 20007.
Barbaccia
M L
ML
Alho
H
H
Costa
E
E
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015152:Blotting, Northern; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016318:Quisqualic Acid; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D005971:Glutamates; D010069:Oxadiazoles; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D011493:Protein Kinase C; D010622:Phencyclidine; D007608:Kainic Acid; D002118:Calcium; D005998:Glycine