Document Detail


The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles.
MedLine Citation:
PMID:  10620485     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies have shown that polychlorinated biphenyls may affect cognitive functions both in human and also in experimental animals. One of the neurochemical parameters that is changed after exposure to these compounds is a reduction in the dopamine level in the brain, although the mechanism behind this reduction is not known. We have therefore investigated whether this reduction could be caused by an effect on vesicular uptake. ortho-Chlorinated biphenyls are found to be competitive inhibitors of dopamine transport into synaptic vesicles from rat brain with K(i) concentrations as low as 4 microM. In contrast, several nonortho-chlorinated biphenyls did not inhibit vesicular uptake. The inhibition was specific for dopamine, in that the uptake of glutamate and GABA was inhibited at higher PCB concentrations under identical conditions. The vesicular Mg-ATPase proton pump was also inhibited at higher concentrations of PCBs than the dopamine transport. Uptake of methylamine gave no indication of any disruption of the vesicular proton gradient. The inhibition of dopamine vesicular uptake by PCBs was competitive. Several of the ortho-PCBs also inhibited the binding of tetrabenazine, which is known to bind to a site close to the dopamine binding site, at the vesicular transporter. The results show that inhibition of vesicular uptake may contribute to the decrease of dopamine reported in nervous tissue after exposure to PCBs under different conditions.
Authors:
E Mariussen; J Morch Andersen; F Fonnum
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  161     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-02-04     Completed Date:  2000-02-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  274-82     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Affiliation:
Norwegian Defence Research Establishment, Kjeller, 2027, Norway. espen.mariussen@ffi.no
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / drug effects*,  metabolism
Dopamine / pharmacokinetics*
Drug Interactions
Enzyme Inhibitors / toxicity
Glutamic Acid / pharmacokinetics
Male
Methylamines / pharmacokinetics
Molecular Structure
Polychlorinated Biphenyls / pharmacology*
Proton-Translocating ATPases / antagonists & inhibitors,  metabolism
Rats
Rats, Wistar
Serotonin / pharmacokinetics
Structure-Activity Relationship
Synaptic Vesicles / drug effects*,  metabolism
Tetrabenazine / metabolism,  pharmacology
Vacuolar Proton-Translocating ATPases*
gamma-Aminobutyric Acid / pharmacokinetics
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Methylamines; 0/Polychlorinated Biphenyls; 50-67-9/Serotonin; 56-12-2/gamma-Aminobutyric Acid; 56-86-0/Glutamic Acid; 58-46-8/Tetrabenazine; 74-89-5/methylamine; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases; EC 3.6.3.14/Proton-Translocating ATPases

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


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