Glutamine synthetase enhances the clearance of extracellular glutamate by the neural retina
- 17 October 2002
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 83 (3), 574-580
- https://doi.org/10.1046/j.1471-4159.2002.01168.x
Abstract
Clearance of synaptic glutamate by glial cells is required for the normal function of excitatory synapses and for prevention of neurotoxicity. Although the regulatory role of glial glutamate transporters in glutamate clearance is well established, little is known about the influence of glial glutamate metabolism on this process. This study examines whether glutamine synthetase (GS), a glial‐specific enzyme that amidates glutamate to glutamine, affects the uptake of glutamate. Retinal explants were incubated in the presence of [14C]glutamate and glutamate uptake was assessed by measurement of the amount of radioactively labeled molecules within the cells and the amount of [14C]glutamine released to the medium. An increase in GS expression in Müller glial cells, caused by induction of the endogenous gene, did not affect the amount of glutamate accumulated within the cells, but led to a dramatic increase in the amount of glutamine released. This increase, which was directly correlated with the level of GS expression, was dependent on the presence of external sodium ions, and could be completely abolished by methionine sulfoximine, a specific inhibitor of GS activity. Our results demonstrate that GS activity significantly influences the uptake of glutamate by the neural retina and suggest that this enzyme may represent an important target for neuroprotective strategies.Keywords
This publication has 42 references indexed in Scilit:
- Steroid hormone receptors: Many Actors in search of a plotCell, 1995
- Coincidence of L‐glutamate/L‐aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: Evidence for coupling of GLAST and GS in transmitter clearanceJournal of Neuroscience Research, 1995
- Alterations of Müller (glial) cells in dystrophic retinae of RCS ratsJournal of Neurocytology, 1995
- Cell to cell contacts control the transcription activity of the glucocorticoid receptorMolecular Endocrinology, 1994
- Nonvesicular release of neurotransmitterNeuron, 1993
- The Time Course of Glutamate in the Synaptic CleftScience, 1992
- The Role of Glutamate Neurotoxicity in Hypoxic-Ischemic Neuronal DeathAnnual Review of Neuroscience, 1990
- Elevation of the Extracellular Concentrations of Glutamate and Aspartate in Rat Hippocampus During Transient Cerebral Ischemia Monitored by Intracerebral MicrodialysisJournal of Neurochemistry, 1984
- Hydrocortisone-mediated regulation of gene expression in embryonic neural retina: Induction of glutamine synthetaseJournal of Steroid Biochemistry, 1975
- Mechanism of inhibition of glutamine synthetase by methionine sulfoximineBiochemistry, 1969