NMR-SPECTROSCOPY STUDY OF THE EFFECT OF 3-NITROPROPIONIC ACID ON GLUTAMATE METABOLISM IN CULTURED ASTROCYTES

3-Nitropropionic acid (3-NPA) is a selective and irreversible inhibito r of succinate dehydrogenase, The effect of this compound on the metab olism of [U-C-13]glutamate was studied in astrocytes using C-13 nuclea r magnetic resonance spectroscopy, The appearance of [1,2,3-C-13]gluta mate in cell extracts and [1,2,3-C-13]glutamine and [U-C-13]lactate in cell media demonstrated the metabolism of labeled glutamate via the t ricarboxylic acid cycle, Such labeling was observed in the control sit uation and also in cells treated with 3 mM 3-NPA, In the cells treated with 3 mM 3-NPA, however, the labeling was significantly reduced, and with 10 mM 3-NPA no such labeling was observed, Labeled aspartate was observed in untreated cells only, Labeled succinate was not detectabl e under control conditions, but increased dose dependently in the pres ence of 3-NPA, Glutamate uptake and conversion of [U-C-13]glutamate to [U-C-13]glutamine was largely unaffected by 3-NPA, and ATP content wa s unchanged, In a previous study using cerebellar neurons, tricarboxyl ic acid cycle metabolism was blocked with 3 mM 3-NPA, The present resu lts show that astrocyte metabolism is more adaptable to blockade of th e tricarboxylic acid cycle by 3-NPA than neuronal metabolism. (C) 1997 Wiley-Liss, Inc.