Document Detail


Increased synaptosomal dopamine content and brain concentration of paraquat produced by selective dithiocarbamates.
MedLine Citation:
PMID:  12716439     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure to pesticides may be a risk factor for Parkinson's disease based on epidemiologic data in humans, animal models and in vitro studies. Different dithiocarbamate pesticides potentiate the toxicity of both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and paraquat in mouse models of Parkinsonism by an unknown mechanism. This study examined the effects of commercially used dithiocarbamates on [3H]dopamine transport in striatal synaptosomal vesicles and on the concentration of [14C]paraquat in vivo in mice. Different ethylenebis-dithiocarbamates and diethyl-dithiocarbamate increased dopamine accumulation in synaptosomes, whereas dimethyl-dithiocarbamate and methyl-dithiocarbamate did not. Increased dopamine accumulation in synaptosomes was dose dependent and was related to the carbon backbone of these molecules. The dithiocarbamates that increased accumulation of dopamine did not alter the influx of dopamine, but rather delayed the efflux out of synaptosomes. These same dithiocarbamates also increased the tissue content of [14C]paraquat in vivo by a mechanism that appeared to be distinct from the dopamine transporter. There was a consistent relationship between the dithiocarbamates that increased synaptosomal accumulation of dopamine and tissue content of paraquat, with those previously demonstrated to enhance paraquat toxicity in vivo. These results suggest that selective dithiocarbamates may alter the kinetics of different endogenous and exogenous compounds to enhance their neurotoxicity.
Authors:
Brian K Barlow; Mona J Thiruchelvam; Lisa Bennice; Deborah A Cory-Slechta; Nazzareno Ballatori; Eric K Richfield
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  85     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-28     Completed Date:  2003-06-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1075-86     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport / drug effects
Brain / metabolism*
Brain Chemistry / drug effects*
Cocaine / pharmacology
Dopamine / analysis,  metabolism*,  pharmacokinetics
Dopamine Plasma Membrane Transport Proteins
Dose-Response Relationship, Drug
Ethylenebis(dithiocarbamates) / pharmacokinetics,  pharmacology
Male
Membrane Glycoproteins*
Membrane Transport Proteins / metabolism
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins*
Organ Specificity
Organometallic Compounds / pharmacokinetics,  pharmacology
Paraquat / analysis*,  pharmacokinetics
Pesticides / pharmacokinetics,  pharmacology
Synaptosomes / chemistry,  drug effects,  metabolism*
Thiocarbamates / pharmacokinetics,  pharmacology*
Grant Support
ID/Acronym/Agency:
ES 01247/ES/NIEHS NIH HHS; ES 05017/ES/NIEHS NIH HHS; ES 05905/ES/NIEHS NIH HHS; ES 06484/ES/NIEHS NIH HHS; ES 11839/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Plasma Membrane Transport Proteins; 0/Ethylenebis(dithiocarbamates); 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/Organometallic Compounds; 0/Pesticides; 0/Thiocarbamates; 0/manganese ethylenebis(dithiocarbamate); 4685-14-7/Paraquat; 50-36-2/Cocaine

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


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