Differential effect of beta-N-oxalylamino-L-alanine, the Lathyrus sativus neurotoxin, and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate on the excitatory amino acid and taurine levels in the brain of freely moving rats

We studied the effect of beta-oxalylamino-L-alanine, a glutamate analog pre sent in Lathyrus sativus seeds and implicated in the etiopathogenesis of ne urolathyrism, and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionat e on the extracellular levels of aspartate, glutamate and taurine in the pr imary motor cortex of freely moving rats. We found that while both neurotox ins increase the level of aspartate and glutamate, only (+/-)-alpha-amino-3 -hydroxy-5-methylisoxazole-4-propionate is able to modulate the level of ta urine. GYKI-52466, a non-competitive non-NMDA antagonist, inhibited beta-ox alylamino-L-alanine-induced increase of aspartate, but not that of glutamat e. Conversely, this antagonist proved to be very efficient in blocking the stimulating effect of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole on all three amino acids. We suggest that beta-oxalylamino-L-alanine increases the level of glutamate in vivo by a mechanism not connected to its effect on the non-NMDA recepto rs, which might involve the inhibition of glutamate transport. This would a llow the excitatory neurotransmitter to reach a concentration sufficient to stimulate the non-NMDA receptors, which in their turn mediate the specific release of aspartate. Although the role of aspartate as a neurotransmitter is still under discussion, it might indeed amplify the excitotoxic cascade through its action on NMDA receptors. We speculate that this sequence of e vents might represent an important step in the molecular cascade leading to the appearance of the selective motoneuron degeneration in neurolathyrism. (C) 2000 Elsevier Science Ltd. All rights reserved.