Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: immunogold evidence from hippocampal slice cultures

J Neurochem. 1995 Aug;65(2):871-81. doi: 10.1046/j.1471-4159.1995.65020871.x.


The immunogold labeling for glutamate and glutamine was studied at the electron microscopic level in hippocampal slice cultures following inhibition of L-glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming); EC]. In control cultures, glutamate-like immunoreactivity was highest in terminals, intermediate in pyramidal cell bodies, and low in glial cells. Glutamine-like immunoreactivity was high in glial cells, intermediate in pyramidal cell bodies, and low in terminals. After inhibition of glutamine synthetase with L-methionine sulfoximine, glutamate-like immunoreactivity was reduced by 52% in terminals and increased nearly four-fold in glia. Glutamine-like immunoreactivity was reduced by 66% in glia following L-methionine sulfoximine, but changed little in other compartments. In cultures that were treated with both L-methionine sulfoximine and glutamine (1.0 mM), glutamate-like immunoreactivity was maintained at control levels in terminals, whereas in glia glutamate-like immunoreactivity was increased and glutamine-like immunoreactivity was decreased to a similar extent as in cultures treated with L-methionine sulfoximine alone. We conclude that (a) glutamate accumulates in glia when the flux through glutamine synthetase is blocked, emphasizing the importance of this pathway for the handling of glutamate; and (b) glutamine is necessary for the maintenance of a normal level of glutamate in terminals, and neither reuptake nor de novo synthesis through pathways other than the glutaminase reaction is sufficient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Culture Techniques
  • Glutamic Acid / metabolism*
  • Glutamine / physiology*
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Immune Sera
  • Immunohistochemistry
  • Male
  • Microscopy, Electron
  • Nerve Endings / metabolism*
  • Neuroglia / metabolism*
  • Rats
  • Rats, Wistar


  • Immune Sera
  • Glutamine
  • Glutamic Acid