Receptor Interactions of Beta-N-oxalyl-L-alpha,beta-diaminopropionic Acid, the Lathyrus Sativus Putative Excitotoxin, with Synaptic Membranes

Direct evidence for the excitotoxicity of 3-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), the Lathyrus sativus neurotoxin has been studied by examining the binding of chemically synthesized [2,3 3H]ODAP ([3H]ODAP) to synaptic membranes. [3H]ODAP binding to membranes was mostly nonspecific, with only a very low specific binding (15-20% of the total binding) and was also not saturable. The low specific binding of [3H]ODAP remained unaltered under a variety of assay conditions. A low Bmax of 3.2 +/- 0.4 pmol/mg and Kd 0.2 +/- 0.08 microM could be discerned for the high affinity interactions under conditions wherein more than 80-90% of the binding was nonspecific. While ODAP could inhibit the binding of [3H]glutamate to chick synaptic membranes with a Ki of 10 +/- 0.9 microM, even L-DAP, a non neurotoxic amino acid was also equally effective in inhibiting the binding of [3H]glutamate. The very low specific binding of [3H]ODAP to synaptic membranes thus does not warrant considering its interactions at glutamate receptors as a significant event. The results thus suggest that the reported in vitro excitotoxic potential of ODAP may not reflect its true mechanism of neurotoxicity.