Glutamine synthetase inhibition prevents cerebral oedema during hyperammonemia.
The relationship between cerebral oedema and cerebral glutamine accumulation was investigated during acute hyperammonemia in anesthetized rats. Six hours of ammonium acetate infusion resulted in an increase in cortical glutamine concentration and a decrease in specific gravity. Pretreatment with methionine sulfoximine inhibited glutamine synthetase, prevented the increase in glutamine during hyperammonemia, and prevented the decrease in specific gravity. We conclude that the increase in brain water content is linked to the glutamine accumulation derived from the detoxification of ammonia by glutamine synthetase.
Takahashi
H
H
Department of Anesthesiology/Critical Care Medicine, and Pediatrics, Johns Hopkins Medical Institution, Baltimore, Maryland.
Koehler
R C
RC
Brusilow
S W
SW
Traystman
R J
RJ
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000641:Ammonia / Q000097:blood*; D000818:Animals; D001929:Brain Edema / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D005973:Glutamine / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013046:Specific Gravity
D000085:Acetates; D005973:Glutamine; D008717:Methionine Sulfoximine; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase; D019342:Acetic Acid; C018824:ammonium acetate