ACTION OF BETA-N-OXALYLAMINO-L-ALANINE ON MOUSE-BRAIN NADH-DEHYDROGENASE ACTIVITY

beta-N-Oxalylamino-L-alanine (L-BOAA), a nonprotein neuroexcitatory am ino acid present in the seeds of Lathyrus sativus (chickling or grass pea), is known to produce its neurotoxic effects by overstimulation of non-N-methyl-D-aspartate receptors, especially lpha-amino-3-hydroxy-5 -methylisoxazole-4-propionic acid (AMPA) receptors, at micromolar conc entrations, It has recently been reported that L-BOAA selectively inhi bits mitochondrial enzyme NADH-dehydrogenase (NADH-DH) in brain slices at subpicomolar concentrations. The present study finds that up to 4 mM concentrations of pure L-BOAA fail to inhibit NADH-DH activity in m ouse brain homogenate and isolated brain mitochondria. Two known inhib itors (rotenone and 1-methyl-4-phenylpyridinium ion, MPP(+)) of this m itochondrial enzyme produced significant inhibition under identical co nditions. NADH-DH inhibition was also not observed in the homogenate o r mitochondria from the brains of animals systemically treated with co nvulsive doses of L-BOAA. Some inhibition (20-37%) of NADH-DH activity was observed in mouse brain slices incubated with 100-1,000 mu M conc entrations of L-BOAA for 1 h at 37 degrees C in an atmosphere of 95% O -2 and 5% CO2, but the inhibition was nonselective, because the activi ty of another mitochondrial enzyme, succinic dehydrogenase, was simila rly inhibited by L-BOAA. These results are in contrast with the report that L-BOAA inhibits mitochondrial NADH-DH selectively at subpicomola r concentrations. We suggest the observed nonselective NADH-DH inhibit ion in mouse brain slices treated with L-BOAA is caused by neuronal da mage through an excitotoxic mechanism.