Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways

Neuron. 1993 Jan;10(1):31-41. doi: 10.1016/0896-6273(93)90239-n.


N-Methyl-D-aspartate (NMDA) or non-NMDA receptor activation is sufficient to induce transcription of the immediate early gene c-fos in a calcium-requiring manner. We sought to determine whether the calcium-dependent mechanisms inducing c-fos transcription are identical following activation of these two receptor subtypes. We used in situ hybridization and fura-2 imaging to detect c-fos mRNA and intracellular calcium in individual dentate gyrus neurons maintained in vitro. Structurally distinct inhibitors of phospholipase A2 and cyclooxygenase abolished NMDA--but not kainic acid-induced increases of c-fos mRNA. Conversely, the calmodulin antagonist calmidazolium markedly inhibited kainic acid--but not NMDA-mediated increases of c-fos mRNA. We propose that the dissociation in the mechanisms transducing the calcium influx signals to the nucleus following NMDA and non-NMDA receptor activation is due to spatially distinct sites of calcium entry, resulting in activation of different enzymes located at distinct sites in the cell.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / pharmacology*
  • Calmodulin / antagonists & inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Genes, fos / genetics*
  • Hippocampus / metabolism
  • Imidazoles / pharmacology
  • In Situ Hybridization
  • Kainic Acid / pharmacology
  • N-Methylaspartate / pharmacology
  • Neurons / metabolism
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A2
  • Protein Kinases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Glutamate / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Signal Transduction / physiology*
  • Transcription, Genetic* / drug effects


  • Calmodulin
  • Cyclooxygenase Inhibitors
  • Imidazoles
  • RNA, Messenger
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • calmidazolium
  • N-Methylaspartate
  • Protein Kinases
  • Phospholipases A
  • Phospholipases A2
  • Kainic Acid
  • Calcium