In vitro toxicological investigations of isoxazolinone amino acids of Lathyrus sativus

M. Riepe, Peter Spencer, F. Lambein, A. C. Ludolph, Charles Allen

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Two non-protein amino acids of lathyrus sativus, β-(isoxazoline-5-on-2-yl)-alanine (BIA) and its higher homologue α-amino-γ-(isoxazoline-5-on-2-yl)-alanine (ACl) were tested for excitotoxic potential. BIA (0.5-2.0 mM) but not ACl (2.0 mM) produced a concentration-dependent neurodegeneration in mouse cortical explants. The neuronal damage was prevented by the prior and simultaneous application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), indicating that it was mediated by non-N-methyl-D-aspartate type receptors. BIA (0.5-2.0 mM) activated CNQX-sensitive currents which were significantly smaller than those activated by 3-N-oxalyl-L-2,3-diaminopropanoic acid (β-ODAP) or α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) in the majority of neurons. In a small number of cells, BIA (2 mM) produced currents which were similar in amplitude to those activated by β-ODAP (50 μM). These results suggest that lathyrus sativus plants engineered to block the synthesis of β-ODAP may accumulate a neurotoxic precursor and therefore must be tested for the presence of both BIA and β-ODAP.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalNatural Toxins
Volume3
Issue number1
DOIs
StatePublished - 1995

Fingerprint

Lathyrus
Toxicology
Amino Acids
Alanine
6-Cyano-7-nitroquinoxaline-2,3-dione
Isoxazoles
D-Aspartic Acid
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neurons
Cell Count
oxalyldiaminopropionic acid
In Vitro Techniques

Keywords

  • α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPA
  • β-oxalylamino-alanine BOAA
  • 3-N-oxalyl-L-2,3-diaminopropanoic acid β-ODAP
  • Excitotoxicity
  • Hippocampal cultures
  • Lathyrism

ASJC Scopus subject areas

  • Toxicology

Cite this

In vitro toxicological investigations of isoxazolinone amino acids of Lathyrus sativus. / Riepe, M.; Spencer, Peter; Lambein, F.; Ludolph, A. C.; Allen, Charles.

In: Natural Toxins, Vol. 3, No. 1, 1995, p. 58-64.

Research output: Contribution to journalArticle

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