Alteration of Striatal Glutamate Release After Glutamine Synthetase Inhibition

Jeffrey D. Rothstein, Boris Tabakoff

Research output: Contribution to journalArticle

Abstract

Abstract: The effect of the glutamine synthetase (GS) inhibitor, methionine sulfoximine (MSO), on glutamate levels in, and glutamate release from, rat striatal tissue was examined. Tissue levels of glutamate were unchanged 24 h after an intraventricular injection of MSO, but tissue glutamine levels were decreased 50%. Calcium‐dependent, potassium‐stimulated glutamate release was diminished in tissue prisms from animals pretreated with MSO compared to controls. The decreased release of glutamate correlated over time with the inhibition of GS following an intraventricular injection of MSO. The maximum diminution of calcium‐dependent, potassium‐stimulated glutamate release (50%) and the maximum inhibition of GS activity (51%) were observed 24 h after MSO. The addition of 0.5 mM glutamine to the perfusion medium completely reversed the effects of MSO pretreatment on calcium‐dependent, potassium‐stimulated glutamate release. Since GS is localized in glial cells and the measured glutamate release is presumed to occur from neurons, the data support the contention that astroglial glutamine synthesis is an important contributor to normal neuronal neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)1438-1446
Number of pages9
JournalJournal of Neurochemistry
Volume43
Issue number5
DOIs
StatePublished - Nov 1984

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Keywords

  • Glutamate
  • Glutamate release
  • Glutamine
  • Glutamine synthetase
  • Methionine sulfoximine
  • Neuron‐glial interactions

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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