Effect of β-N-oxalyl-L-α, β-diaminopropionic acid on glutamate uptake by synaptosomes

Abstract

THE unusual amino acid β-N-oxalyl-L-α, β-diaminopropionic acid (ODAP), isolated from the seeds of Lathyrus sativus is a potent neurotoxin^1–3. It produces biochemical changes in the brain typical of an excitant amino acid and is implicated in the aetiology of human neurolathyrism caused by eating the seeds of L. sativus^4–6. It may act as a glutamate antagonist: ODAP inhibits glutamate oxidation⁷ possibly by inhibiting glutamate uptake in bovine brain mitochondria; it also acts as a competitive inhibitor of glutamate uptake in certain strains of yeast⁸, and a similar process might occur at the synaptic level. Any effect of ODAP on glutamate uptake at synapses is significant in view of the neurotransmitter function of glutamate, which seems to be neuroexcitory as well as neurotoxic^9–12. But Balcar and Johnston¹³ have shown with rat brain slices that ODAP does not inhibit the glutamate uptake by the high affinity system.