β-cyano-L-alanine toxicity

Evidence for the involvement of an excitotoxic mechanism

D. N. Roy, M. I. Sabri, R. J. Kayton, Peter Spencer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The legume Vicia sativa (common vetch) harbors the neurotoxic nonprotein amino acid β-cyano-L-alanine (BCLA) and its γ-glutamyl derivative. BCLA elicits hyperexcitability, convulsions, and rigidity in chicks and rats after oral or intraperitoneal administration, but the mechanism of its action is unknown. The effect of different concentrations of BCLA (0.075-10.0 mM) has been investigated in an organotypic tissue culture system. BCLA concentrations of 0.075 and 0.60 mM had no effect, even up to 6 hr. No changes were observed in cultures treated with 1 mM BCLA for 4 hr. BCLA (2.0-10.0 mM) induces concentration-dependent changes in the explants. The explants display neuronal vacuolation, chromatin clumping, and dense shrunken cells, a pathological response generally seen with excitotoxin. MK-801 (35 μM), which blocks the open ion channel associated with the N-methyl-D-aspartate (NMDA) class of glutamate receptors, attenuates the neurotoxic property of BCLA, while the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 μM), provides no significant protection. Treatment of isolated mouse brain mitochondria with up to 5 mM BCLA had no inhibitory effect on the activity of NADH-dehydrogenase (complex 1) or cytochrome c oxidase (complex IV), a cyanide-sensitive enzyme. These results suggest that the neurotoxicity of BCLA (or derivative) is mediated directly or indirectly through NMDA receptors.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalNatural Toxins
Volume4
Issue number6
StatePublished - 1996

Fingerprint

Vicia sativa
Alanine
Toxicity
6-Cyano-7-nitroquinoxaline-2,3-dione
Derivatives
Electron Transport Complex I
D-Aspartic Acid
Tissue culture
Mitochondria
Dizocilpine Maleate
Neurotoxins
Glutamate Receptors
Cyanides
Electron Transport Complex IV
N-Methylaspartate
Ports and harbors
N-Methyl-D-Aspartate Receptors
Ion Channels
Fabaceae
Rigidity

Keywords

  • β-Cyano-L-alanine
  • Excitotoxicity
  • Glutamate receptors
  • Neurotoxicity
  • Vicia sativa

ASJC Scopus subject areas

  • Toxicology

Cite this

β-cyano-L-alanine toxicity : Evidence for the involvement of an excitotoxic mechanism. / Roy, D. N.; Sabri, M. I.; Kayton, R. J.; Spencer, Peter.

In: Natural Toxins, Vol. 4, No. 6, 1996, p. 247-253.

Research output: Contribution to journalArticle

Roy, D. N. ; Sabri, M. I. ; Kayton, R. J. ; Spencer, Peter. / β-cyano-L-alanine toxicity : Evidence for the involvement of an excitotoxic mechanism. In: Natural Toxins. 1996 ; Vol. 4, No. 6. pp. 247-253.
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