Document Detail


Beta-N-methylamino-L-alanine neurotoxicity: requirement for bicarbonate as a cofactor.
MedLine Citation:
PMID:  3136549     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ingestion of the excitotoxic cycad seed amino acid beta-N-methylamino-L-alanine may be responsible for the neuronal degeneration associated with Guam amyotrophic lateral sclerosis-parkinsonism-dementia in man. However, the basis for the central neurotoxicity of beta-N-methylamino-L-alanine has been unclear, as it lacks the omega acidic (or equivalent electronegative) moiety characteristic of other excitatory amino acids. beta-N-methylamino-L-alanine produced neurotoxic and neuroexcitatory effects in murine cortical cell cultures only when physiological concentrations of bicarbonate were available in the extracellular bathing medium. Bicarbonate may interact noncovalently with beta-N-methylamino-L-alanine to produce, in combination, a molecular configuration that activates glutamate receptors.
Authors:
J H Weiss; D W Choi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  241     ISSN:  0036-8075     ISO Abbreviation:  Science     Publication Date:  1988 Aug 
Date Detail:
Created Date:  1988-09-19     Completed Date:  1988-09-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  973-5     Citation Subset:  IM    
Affiliation:
Department of Neurology, Stanford University Medical Center, Stanford 94305.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids, Diamino / toxicity*
Animals
Bicarbonates / metabolism*
Cells, Cultured
Cerebral Cortex / drug effects*
Electrophysiology
Hydrogen-Ion Concentration
Mice
Microelectrodes
Neurons / drug effects*
Oxadiazoles / toxicity
Quisqualic Acid
beta-Alanine / analogs & derivatives,  toxicity
Grant Support
ID/Acronym/Agency:
NS12151/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids, Diamino; 0/Bicarbonates; 0/Oxadiazoles; 107-95-9/beta-Alanine; 16676-91-8/alpha-amino-beta-methylaminopropionate; 52809-07-1/Quisqualic Acid; 7554-90-7/oxalyldiaminopropionic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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