Document Detail


The importance of glutamate, glycine, and gamma-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity.
MedLine Citation:
PMID:  15845423     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Historically, amino acids were studied in the context of their importance in protein synthesis. In the 1950s, the focus of research shifted as amino acids were recognized as putative neurotransmitters. Today, many amino acids are considered important neurochemicals. Although many amino acids play a role in neurotransmission, glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid (GABA) are among the more prevalent and better understood. Glu, the major excitatory neurotransmitter, and Gly and GABA, the major inhibitory neurotransmitters, in the central nervous system, are known to be tightly regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn), mercury (Hg), or lead (Pb), however, can lead to dysregulation of these neurochemicals and subsequent neurotoxicity. While the ability of these metals to disrupt the regulation of Glu, Gly and GABA have been studied, few articles have examined the collective role of these amino acids in the respective metal's mechanism of toxicity. For each of the neurotransmitters above, we will provide a brief synopsis of their regulatory function, including the importance of transport and re-uptake in maintaining their optimal function. Additionally, the review will address the hypothesis that aberrant homeostasis of any of these amino acids, or a combination of the three, plays a role in the neurotoxicity of Mn, Hg, or Pb.
Authors:
Vanessa A Fitsanakis; Michael Aschner
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  204     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-22     Completed Date:  2005-06-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  343-54     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, B-3307 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232-2495, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Glutamic Acid / metabolism*
Glycine / metabolism*
Humans
Kidney Diseases / chemically induced,  metabolism
Lead Poisoning / metabolism*
Manganese Poisoning / metabolism*
Mercury Poisoning / metabolism*
gamma-Aminobutyric Acid / metabolism*
Chemical
Reg. No./Substance:
56-12-2/gamma-Aminobutyric Acid; 56-40-6/Glycine; 56-86-0/Glutamic Acid

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


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