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

J Neurochem. 1995 Jul;65(1):1-9. doi: 10.1046/j.1471-4159.1995.65010001.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / 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*


  • Adcyap1 protein, mouse
  • Neuropeptides
  • Neurotransmitter Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • RNA, Messenger
  • Vasoactive Intestinal Peptide
  • Glutamic Acid