The neurotoxin, beta-N-methylamino-L-alanine (BMAA) interacts with the strychnine-insensitive glycine modulatory site of the N-methyl-D-aspartate receptor.
Electrophysiological and receptor binding techniques were used to determine whether the neurotoxin beta-N-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 active 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.
Allen
C N
CN
Department of Physiology, Oregon Health Sciences University, Portland 97201, USA.
Omelchenko
I
I
Ross
S M
SM
Spencer
P
P
D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured / Q000187:drug effects; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology*; D013997:Time Factors
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; C001824:beta-N-methylamino-L-alanine; D013331:Strychnine; D005998:Glycine