Lathyrus excitotoxin: mechanism of neuronal excitation by L-2-oxalylamino-3-amino- and L-3-oxalylamino-2-amino-propionic acid.
Intracellular recordings were made in cultured neurones from foetal mouse spinal cord. The effects of applications of the neurotoxin, L-3-oxalylamino-2-amino-propionic acid (a constituent of the chickling pea, Lathyrus sativus) and its 2-oxalylamino isomer on membrane potential and conductance were examined in the presence of TTX and TEA and compared to those of other excitatory amino acids. Although both compounds produced membrane depolarization and an increase in input conductance, the 3-oxalylamino isomer (beta-ODAP) was approximately equal to 10 times more potent than the 2-oxalylamino isomer (alpha-ODAP). beta-ODAP caused a voltage-independent change in conductance, as compared to an apparent voltage-dependent decrease produced in the same neurons by L-aspartic acid (L-ASP). Although reversal potentials determined for beta-ODAP resembled those for alpha-ODAP and kainic acid, they were consistently and significantly lower than the reversal level for L-ASP. Although the receptor antagonist 2-amino-5-phosphonovaleric acid (APV) and the divalent cation Cd2+ did not alter the conductance increase evoked by beta-ODAP, they markedly depressed responses to L-ASP. Such differences suggest a mechanism of excitatory action for the neurotoxin, beta-ODAP, which does not involve a Ca2+-dependent mechanism and is quite different from that for L-ASP and N-methyl-D-aspartic acid, but similar to that of kainic and quisqualic acids.(ABSTRACT TRUNCATED AT 250 WORDS)
D015763:2-Amino-5-phosphonovalerate; D000409:Alanine / Q000031:analogs & derivatives*; D000599:Amino Acids, Diamino / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002478:Cells, Cultured; D007887:Fabaceae / Q000032:analysis*; D005333:Fetus; D007478:Iontophoresis; D051379:Mice; D009498:Neurotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D013116:Spinal Cord / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology
D000599:Amino Acids, Diamino; D009498:Neurotoxins; D002104:Cadmium; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D015763:2-Amino-5-phosphonovalerate; D014633:Valine; D000409:Alanine