| The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles. | |
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MedLine Citation:
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PMID: 10620485 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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E Mariussen; J Morch Andersen; F Fonnum |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 161 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 1999 Dec |
Date Detail:
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Created Date: 2000-02-04 Completed Date: 2000-02-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 274-82 Citation Subset: IM |
Copyright Information:
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Copyright 1999 Academic Press. |
Affiliation:
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Norwegian Defence Research Establishment, Kjeller, 2027, Norway. espen.mariussen@ffi.no |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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