Activation of ionotropic glutamate receptors reduces the production of transforming growth factor-beta2 by developing neurons

Eur J Neurosci. 2000 Dec;12(12):4589-93. doi: 10.1046/j.0953-816x.2000.01354.x.


Neuronal cultures derived from developing rat cerebral cortex were used to investigate the influence of glutamate receptors on the neuronal production of transforming growth factor-beta2 (TGFbeta2), a multifunctional cytokine that modulates neuronal and glial growth. Long-term exposure (48 h) of cortical neurons to selective antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors markedly increased TGFbeta2 levels in the culture medium. Conversely, treatment with NMDA or kainate reduced TGFbeta2 to levels below those in untreated cultures. The effect of kainate did not require NMDA receptor activity. Neuronal depolarization with K+ also reduced TGFbeta2 levels by opening voltage-gated L-type Ca2+ channels. Semi-quantitative RT-PCR measurements of neuronal TGFbeta2 mRNA showed that NMDA or AMPA/kainate receptor stimulation reduced TGFbeta2 mRNA levels. These results demonstrate that tonic activation of glutamate-gated cation channels downregulates neuronal expression of the TGFbeta2 gene and provide evidence for a novel mechanism whereby excitatory amino acids could influence the development of glial and neuronal lineages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology
  • Dizocilpine Maleate / pharmacology
  • Embryo, Mammalian
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Potassium / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Calcium Channels, L-Type
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Glutamate
  • Transforming Growth Factor beta
  • N-Methylaspartate
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Potassium