Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat

@article{WillardMack1996InhibitionOG,
  title={Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat},
  author={Cynthia L Willard-Mack and Raymond C. Koehler and Takahiko Hirata and Linda Collins Cork and H. Takahashi and R. J. Traystman and Saul W. Brusilow},
  journal={Neuroscience},
  year={1996},
  volume={71},
  pages={589-599}
}
Methionine Sulfoximine, a Glutamine Synthetase Inhibitor, Attenuates Increased Extracellular Potassium Activity during Acute Hyperammonemia
TLDR
It is concluded that acute hyperammonemia impairs astrocytic control of [K+]e and that this impairment is linked to glutamine accumulation rather than ammonium ions per se.
Brain Alanine Formation as an Ammonia-Scavenging Pathway during Hyperammonemia: Effects of Glutamine Synthetase Inhibition in Rats and Astrocyte—Neuron Co-Cultures
TLDR
Investigating whether the GS inhibitor methionine sulfoximine (MSO) enhances incorporation of 15NH4+ in alanine during acute hyperammonemia provides evidence that ammonia is detoxified by the concerted action of GDH and ALAT both in vivo and in vitro.
Toxic effects of glutamine in the CNS are triggered by its accumulation in astrocytic mitochondria
TLDR
Evidence that many aspects of ammonia toxicity in HE-affected brain are mediated by glutamine (Gln), synthesized in excess from ammonia and glutamate by glutamines synthetase (GS), an astrocytic enzyme is discussed.
Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells
TLDR
The data suggest that hypoosmolarity accelerates the swelling‐inducing effect of glutamine on retinal glial cells, and that swelling induction by glutamine is mediated by inducing oxidative‐nitrosative stress, inflammatory lipid mediators, and mitochondrial dysfunction.
Dysregulation of Astrocytic Glutamine Transport in Acute Hyperammonemic Brain Edema
TLDR
The changes in glutamine transport link glutaminosis- evoked mitochondrial dysfunction to oxidative-nitrosative stress as formulated in the “Trojan Horse” hypothesis.
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Physiological Levels of Ammonia Regulate Glutamine Synthesis from Extracellular Glutamate in Astrocyte Cultures
TLDR
Ammonia addition stimulates the conversion of glutamate to glutamine in intact astrocyte cultures and glutamine synthesis appears to be limited by the rate of glutamate accumulation and the activity of competing reactions and not by theActivity of glutamine synthetase.
Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats.
TLDR
It is suggested that accumulated glutamine may serve as an idiogenic osmole causing swelling to account for the many pathophysiological abnormalities found during coma associated with various forms of liver disease, inborn errors of metabolism, and Reye's syndrome.
Destabilization of Glial Fibrillary Acidic Protein mRNA in Astrocytes by Ammonia and Protection by Extracellular ATP
TLDR
Treatment of cultured astrocytes with ammonium chloride reduces GFAP mRNA by up to 85% without inhibiting total RNA synthesis, and studies using α‐amanitin, an inhibitor of RNA polymerase II, showed that NH4Cl decreased the stability of GF AP mRNA by ∼50%.
Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats.
TLDR
The grossly abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to glutamine accumulation rather than ammonia per se, although other aspects of astrocyte dysfunction are likely to be important.
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TLDR
It is indicated that ammonia intoxication does not depend upon the mere presence of high cerebral ammonia levels, but is related to the so-called mechanism of detoxication by which ammonia enters into the cerebral metabolic cycles.
Astrocyte swelling in liver failure: role of glutamine and benzodiazepines.
TLDR
These findings implicate glutamine and the peripheral-type benzodiazepine receptor in the pathogenesis of the edema associated with fulminant hepatic failure and diminish many of the effects caused by ammonia.
Morphologic Effects of Ammonia on Primary Astrocyte Cultures. I. Light Microscopic Studies
TLDR
Primary astrocyte cultures derived from neonatal rats were exposed to varying concentrations of ammonia for one to ten days and showed changes proportional to the concentration and duration of ammonia treatment, which show that ammonia is capable of directly causing morphologic alterations inAstrocytes.
Glutamate Increases Glycogen Content and Reduces Glucose Utilization in Primary Astrocyte Culture
TLDR
The glycogen content of astrocytes is linked to the rate of glucose utilization and that glucose utilization can, in turn, be affected by the availability of alternative metabolic substrates, which suggest a mechanism by which brain glycogen accumulation occurs during decreased neuronal activity.
An ultrastructural study of methionine sulphoximine-induced glycogen accumulation in astrocytes of the mouse cerebral cortex
TLDR
Glycogen distribution in the mouse cerebral cortex was examined with electron microscopy following treatment with the experimental convulsant, methionine sulphoximine and it is suggested that the glycogen may be derived from glutamate which under normal conditions would be converted to glutamine.
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