The neurotoxin, β-N-methylamino-l-alanine (BMAA) interacts with the strychnine-insensitive glycine modulatory site of the N-methyl-d-aspartate receptor

Charles Allen, I. Omelchenko, S. M. Ross, Peter Spencer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Electrophysiological and receptor binding techniques were used to determine whether the neurotoxin β-N-4-methylamino-l-alanine (BMAA), a monocarboxylic amino acid, can act at the strychnine-insensitive glycine modulatory site to modify the activity of N-methyl-d-aspartate receptors. dl-BMAA but not l-BMAA reversibly potentiated the amplitude of NMDA-activated currents. Neither dl-BMAA nor l-BMAA were able independently to activate currents. The reversal potential and the potential-dependence of the amplitude were not affected by dl-BMAA. The dl-BMAA effect was reversibly antagonized by 7-chlorokynurenic acid. Concentration jump experiments showed that the time course of the "off" response of NMDA-activated currents in the presence of dl-BMAA is faster than in the presence of glycine, suggesting that dl-BMAA dissociates from the receptor more rapidly than glycine. dl-BMAA produced a concentration-dependent displacement of [3H]glycine binding which was additive with that of 7-chlorokynurenic acid. These data indicate that d-BMAA could act as a stereospecific modulator of NMDA receptor function by acting as an agonist at the strychnine-insensitive glycine modulatory site of the NMDA receptor.

Original languageEnglish (US)
Pages (from-to)651-658
Number of pages8
JournalNeuropharmacology
Volume34
Issue number6
DOIs
StatePublished - 1995

Fingerprint

Strychnine
Neurotoxins
Alanine
Glycine
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
aspartic acid receptor
Amino Acids

Keywords

  • excitotoxicity
  • N-methyl-d-aspartate receptor
  • strychnine-insensitive glycine modulatory site
  • β-N-methylamino-l-alanine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology
  • Drug Discovery

Cite this

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title = "The neurotoxin, β-N-methylamino-l-alanine (BMAA) interacts with the strychnine-insensitive glycine modulatory site of the N-methyl-d-aspartate receptor",
abstract = "Electrophysiological and receptor binding techniques were used to determine whether the neurotoxin β-N-4-methylamino-l-alanine (BMAA), a monocarboxylic amino acid, can act at the strychnine-insensitive glycine modulatory site to modify the activity of N-methyl-d-aspartate receptors. dl-BMAA but not l-BMAA reversibly potentiated the amplitude of NMDA-activated currents. Neither dl-BMAA nor l-BMAA were able independently to activate currents. The reversal potential and the potential-dependence of the amplitude were not affected by dl-BMAA. The dl-BMAA effect was reversibly antagonized by 7-chlorokynurenic acid. Concentration jump experiments showed that the time course of the {"}off{"} response of NMDA-activated currents in the presence of dl-BMAA is faster than in the presence of glycine, suggesting that dl-BMAA dissociates from the receptor more rapidly than glycine. dl-BMAA produced a concentration-dependent displacement of [3H]glycine binding which was additive with that of 7-chlorokynurenic acid. These data indicate that d-BMAA could act as a stereospecific modulator of NMDA receptor function by acting as an agonist at the strychnine-insensitive glycine modulatory site of the NMDA receptor.",
keywords = "excitotoxicity, N-methyl-d-aspartate receptor, strychnine-insensitive glycine modulatory site, β-N-methylamino-l-alanine",
author = "Charles Allen and I. Omelchenko and Ross, {S. M.} and Peter Spencer",
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T1 - The neurotoxin, β-N-methylamino-l-alanine (BMAA) interacts with the strychnine-insensitive glycine modulatory site of the N-methyl-d-aspartate receptor

AU - Allen, Charles

AU - Omelchenko, I.

AU - Ross, S. M.

AU - Spencer, Peter

PY - 1995

Y1 - 1995

N2 - Electrophysiological and receptor binding techniques were used to determine whether the neurotoxin β-N-4-methylamino-l-alanine (BMAA), a monocarboxylic amino acid, can act at the strychnine-insensitive glycine modulatory site to modify the activity of N-methyl-d-aspartate receptors. dl-BMAA but not l-BMAA reversibly potentiated the amplitude of NMDA-activated currents. Neither dl-BMAA nor l-BMAA were able independently to activate currents. The reversal potential and the potential-dependence of the amplitude were not affected by dl-BMAA. The dl-BMAA effect was reversibly antagonized by 7-chlorokynurenic acid. Concentration jump experiments showed that the time course of the "off" response of NMDA-activated currents in the presence of dl-BMAA is faster than in the presence of glycine, suggesting that dl-BMAA dissociates from the receptor more rapidly than glycine. dl-BMAA produced a concentration-dependent displacement of [3H]glycine binding which was additive with that of 7-chlorokynurenic acid. These data indicate that d-BMAA could act as a stereospecific modulator of NMDA receptor function by acting as an agonist at the strychnine-insensitive glycine modulatory site of the NMDA receptor.

AB - Electrophysiological and receptor binding techniques were used to determine whether the neurotoxin β-N-4-methylamino-l-alanine (BMAA), a monocarboxylic amino acid, can act at the strychnine-insensitive glycine modulatory site to modify the activity of N-methyl-d-aspartate receptors. dl-BMAA but not l-BMAA reversibly potentiated the amplitude of NMDA-activated currents. Neither dl-BMAA nor l-BMAA were able independently to activate currents. The reversal potential and the potential-dependence of the amplitude were not affected by dl-BMAA. The dl-BMAA effect was reversibly antagonized by 7-chlorokynurenic acid. Concentration jump experiments showed that the time course of the "off" response of NMDA-activated currents in the presence of dl-BMAA is faster than in the presence of glycine, suggesting that dl-BMAA dissociates from the receptor more rapidly than glycine. dl-BMAA produced a concentration-dependent displacement of [3H]glycine binding which was additive with that of 7-chlorokynurenic acid. These data indicate that d-BMAA could act as a stereospecific modulator of NMDA receptor function by acting as an agonist at the strychnine-insensitive glycine modulatory site of the NMDA receptor.

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KW - N-methyl-d-aspartate receptor

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KW - β-N-methylamino-l-alanine

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