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Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide potentiate c-fos expression induced by glutamate in cultured cortical neurons

By J. L. Martin, D. Gasser and P. J. Magistretti


Previous reports have demonstrated that glutamate stimulates c-fos mRNA expression in primary cultures of mouse cerebral cortical neurons. We show here that vasoactive intestinal peptide (VIP) induces c-fos mRNA expression; however, this effect of VIP is completely inhibited by the noncompetitive NMDA receptor antagonist MK-801, therefore indicating that VIP stimulates c-fos expression in a glutamate-dependent manner. A similar effect was observed with pituitary adenylate cyclase-activating polypeptide27 (PACAP27). At the intracellular level, coactivation of protein kinases A and C mediates the glutamate-dependent stimulation of c-fos expression evoked by VIP, because either H-89 or staurosporin inhibits the effect of VIP as well as that of glutamate. These results point to a "biochemical AND gate" mechanism, which implies the obligatory activation of both protein kinases A and C in the transduction of c-fos expression. In summary, this article provides evidence that VIP and PACAP27 potentiate the effect of glutamate, the principal effector on c-fos expression, suggesting that both peptides can increase the "throughput" or "strength" of glutamate-containing circuits in the cerebral cortex

Topics: Animals Cerebral Cortex/cytology/*physiology Drug Synergism Gene Expression/*drug effects Genes, fos/*drug effects Glutamic Acid/*pharmacology Mice Mice, Inbred Strains Neurons/physiology Neuropeptides/*pharmacology Neurotransmitter Agents/pharmacology Pituitary Adenylate Cyclase-Activating Polypeptide RNA, Messenger/metabolism Vasoactive Intestinal Peptide/*pharmacology
Year: 1995
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