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.
Department of Biochemistry, O.U, Hyderabad, India.
R K
RK
Jain
M A
MA
Junaid
S L
SL
Rao
D000599:Amino Acids, Diamino / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002645:Chickens; D007887:Fabaceae; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000493:pharmacokinetics* / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*
D000599:Amino Acids, Diamino; D009498:Neurotoxins; D017470:Receptors, Glutamate; C100126:oxalyldiaminopropionic acid; D018698:Glutamic Acid