TY - JOUR T1 - In primary cultures of cerebellar granule cells the activation of N-methyl-D-aspartate-sensitive glutamate receptors induces c-fos mRNA expression. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 401 LP - 408 VL - 35 IS - 4 AU - A M Szekely AU - M L Barbaccia AU - H Alho AU - E Costa Y1 - 1989/04/01 UR - http://molpharm.aspetjournals.org/content/35/4/401.abstract N2 - 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. ER -