L-Methionine-DL-sulfoximine induces massive efflux of glutamine from cortical astrocytes in primary culture

L-Methionine-DL-sulfoximine (MSO) is a potent convulsant which metabolically and morphologogically primarily affects astroglia, and the links between the gliotoxic and neurophysiological effects of MSO are not clear. A 5 min treatment with 3 mM MSO increased the rate of efflux of newly loaded radiolabelled glutamine (Gln) from rat cortical astrocytes in primary culture to more than 400% of the basal efflux. MSO did not affect the efflux of the neurotransmitter amino acids GABA or D-aspartate (a non-metabolizable analogue of L-glutamate), under the same experimental conditions. MSO-induced overflow with Gln, which according to a recent account strongly interacts with the N-methyl-D-aspartate (NMDA) receptor complex, may contribute to the convulsive action of the drug.