Beta-N-methylamino-L-alanine in the presence of bicarbonate is an agonist at non-N-methyl-D-aspartate-type receptors.
Beta-N-Methylamino-L-alanine, a component of the neurotoxic Cycas circinalis plant, activates an ionic current which is antagonized by extracellular Ca2+ but not by the excitatory amino acid receptor antagonists D,L-2-amino-5-phosphonovalerate (10-100 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (1-10 microM). This current was reduced by 50% in 0.5 mM extracellular Ca2+ and 92% in 3.0 mM Ca2+ when compared to those recorded in 0.1 mM Ca2+. Addition of 10 or 20 mM NaHCO3 to beta-N-methylamino-L-alanine (500 microM) potentiated the currents 224% and 578%, respectively. Addition of NaHCO3 to the extracellular Ringers (pH 7.2) shifted the pH to 7.7 (10 mM) or 8.3 (20 mM). beta-N-Methylamino-L-alanine was potentiated by NaHCO3 at pH 7.2, 7.7 and 8.3, but the potentiation with NaHCO3 (20 mM) was larger at pH 8.3 (5.7-fold) compared to pH 7.2 (3-fold). NaHCO3 (20 mM) had no effect on quisqualate-, N-methyl-D-aspartate- or kainate-activated ionic currents. The beta-N-methylamino-L-alanine-NaHCO3-activated currents were reduced 49% by 1 microM and 80% by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione suggesting an agonist action at non-N-methyl-D-aspartate-type receptors. Activity at N-methyl-D-aspartate receptors is unlikely since the beta-N-methylamino-L-alanine-NaHCO3 currents are not antagonized by D,L-2-amino-5-phosphonovalerate (10-100 microM), potentiated by addition of glycine (10 microM) or blocked by extracellular Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Allen
C N
CN
Center for Research on Environmental and Occupational Toxicology, Oregon Health Sciences University, Portland 97201-3098.
Spencer
P S
PS
Carpenter
D O
DO
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000599:Amino Acids, Diamino / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D000087522:Cyanobacteria Toxins; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D000599:Amino Acids, Diamino; D001639:Bicarbonates; D000087522:Cyanobacteria Toxins; D007473:Ion Channels; D009498:Neurotoxins; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; C001824:beta-N-methylamino-L-alanine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium