Methionine Sulfoximine, a Glutamine Synthetase Inhibitor, Attenuates Increased Extracellular Potassium Activity during Acute Hyperammonemia
-
- Hideyoshi Sugimoto
- Department of Anesthesiology/Critical Care Medicine and Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
-
- Raymond C. Koehler
- Department of Anesthesiology/Critical Care Medicine and Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
-
- David A. Wilson
- Department of Anesthesiology/Critical Care Medicine and Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
-
- Saul W. Brusilow
- Department of Anesthesiology/Critical Care Medicine and Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
-
- Richard J. Traystman
- Department of Anesthesiology/Critical Care Medicine and Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
抄録
<jats:p>Hyperammonemia causes glutamine accumulation and astrocyte swelling. Inhibition of glutamine synthesis reduces ammonia-induced edema formation and watery swelling in astrocyte processes. Ordinarily, astrocytes tightly control extracellular K<jats:sup>+</jats:sup>activity [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>. We tested the hypothesis that acute hyperammonemia interferes with this tight regulation such that [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>increases and that inhibition of glutamine synthetase reduces this increase in [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>. Ion-sensitive microelectrodes were used to measure [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>in parietal cortex continuously over a 6-h period in anesthetized rats. After i.v. sodium acetate infusion in eight control rats, plasma ammonia concentration was 33 ± 26 μmol/L (± SD) and [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>remained stable at 4.3 ± 1.6 mmol/L. During ammonium acetate infusion in nine rats, plasma ammonia increased to 594 ± 124 μmol/L at 2 h and to 628 ± 135 μmol/L at 6 h. There was a gradual increase in [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>from 3.9 ± 0.7 to 6.8 ± 2.7 mmol/L at 2 h and 11.8 ± 6.7 mmol/L at 6 h. In eight rats, L-methionine-D,L-sulfoximine (150 mg/kg) was infused 3 h before ammonium acetate infusion to inhibit glutamine synthetase. At 2 and 6 h of ammonium acetate infusion, plasma ammonia concentration was 727 ± 228 and 845 ± 326 μmol/L, and [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>was 4.5 ± 1.9 and 6.1 ± 3.8 mmol/L, respectively. The [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>value at 6 h was significantly less than that obtained with ammonium acetate infusion alone but was not different from that obtained with sodium acetate infusion. We conclude that acute hyperammonemia impairs astrocytic control of [K<jats:sup>+</jats:sup>]<jats:sub>e</jats:sub>and that this impairment is linked to glutamine accumulation rather than ammonium ions per se.</jats:p>
収録刊行物
-
- Journal of Cerebral Blood Flow & Metabolism
-
Journal of Cerebral Blood Flow & Metabolism 17 (1), 44-49, 1997-01
SAGE Publications
- Tweet
詳細情報
-
- CRID
- 1363388843675972096
-
- NII論文ID
- 30009334938
-
- ISSN
- 15597016
- 0271678X
-
- データソース種別
-
- Crossref
- CiNii Articles