Possible Interaction: Glutamine and Buthionine Sulfoximine

“Experimentally, inhibition of glutamine synthesis with methionine-sulfoximine (MSO) prevents the development of ammoniainduced brain edema in normal rats (5), decreases astrocyte swelling (6) and ameliorates brain edema in rats after portacaval anastomosis (PCA) receiving an ammonia infusion (7).”

“While inhibitors of brain glutamine synthesis such as methionine sulfoximine , have been proposed for the prevention of brain edema in ALF, potential adverse effects have so far limited their applicability.”

“We used an inhibitor of L-glutamine synthesis L-methionine sulfoximine - MSO) to promote a further reduction in intracellular L-glutamine levels.”

“Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of 15NH4+ into glutamine in all tissues.”

“ Glutamine synthetase inhibition with MSO significantly decreased glutamine formation.”

“Methionine sulfoximine decreased to undetectable levels the fractional 13C enrichment in the carbons of cerebral glutamine in both groups and had no significant effect on 13C incorporation in glutamate and GABA, suggesting that glutamine is not the main precursor of glutamate and GABA.”

“Administration of MSO resulted in a 40% decrease in plasma glutamine and a 60% decrease in intracellular muscle glutamine, both of which were successfully attenuated by glutamine infusions.”

“ L-methionine sulfoximine (1-10 mM) was added to superfusion media to inhibit glutamine synthetase, a Müller cell specific enzyme, by more than 99% within 5-10 min, thereby disrupting the conversion of glutamate to glutamine in the Müller cells.”

“Methionine sulphoximine treatment for 4 days resulted in a 50% decrease in arterial glutamine concentration.”

“The content of glutamine was reduced markedly by omission of either glutamate or ammonium from the incubation solution, or by inhibition of glutamine synthetase activity with methionine sulfoximine.”