HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity.

Abstract
CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
AuthorsJ Zhang, Y Su, T D Oury, C A Piantadosi
JournalBrain research (Brain Res) Vol. 606 Issue 1 Pg. 56-62 (Mar 19 1993) ISSN: 0006-8993 [Print] Netherlands
PMID8462004 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amino Acids
  • Monoamine Oxidase Inhibitors
  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • Pargyline
  • Oxygen
  • Norepinephrine
Topics
  • Amino Acids (metabolism)
  • Animals
  • Arginine (analogs & derivatives, pharmacology)
  • Brain (drug effects, metabolism)
  • Hyperbaric Oxygenation
  • Male
  • Monoamine Oxidase Inhibitors (pharmacology)
  • Nitric Oxide (metabolism)
  • Nitroarginine
  • Norepinephrine (metabolism)
  • Osmolar Concentration
  • Oxygen (adverse effects)
  • Pargyline (pharmacology)
  • Rats
  • Rats, Sprague-Dawley

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: