Suppression of the enzymes of glutamate metabolism in cortical synaptosomes in methionine sulfoximine toxicity.

Enzymes of glutamate metabolism were studied in synaptosomes prepared from normal rats and those treated with acute (300 mg/kg) and subacute (150 mg/kg) doses of the convulsant methionine sulfoximine (MSO). The activities of glutamine synthetase, glutamate dehydrogenase and aspartate aminotransferase were inhibited in the synaptosomes of drug treated animals. It is suggested that MSO would suppress the formation of glutamine and glutamate and consequently the releasable pool of glutamate, aspartate and GABA. These neurotransmitters would be depleted from the nerve endings. It is also indicated that the ammonia accumulated would affect the cerebral functioning by interfering with the maintenance of ionic gradients.