Document Detail

Modification of dopamine transporter function: effect of reactive oxygen species and dopamine.
MedLine Citation:
PMID:  8764584     Owner:  NLM     Status:  MEDLINE    
Dopamine can oxidize to form reactive oxygen species and quinones, and we have previously shown that dopamine quinones bind covalently to cysteinyl residues on striatal proteins. The dopamine transporter is one of the proteins at risk for this modification, because it has a high affinity for dopamine and contains several cysteinyl residues. Therefore, we tested whether dopamine transport in rat striatal synaptosomes could be affected by generators of reactive oxygen species, including dopamine. Uptake of [3H]dopamine (250 nM) was inhibited by ascorbate (0.85 mM; -44%), and this inhibition was prevented by the iron chelator diethylenetriaminepentaacetic acid (1 mM), suggesting that ascorbate was acting as a prooxidant in the presence of iron. Preincubation with xanthine (500 microM) and xanthine oxidase (50 mU/ml) also reduced [3H]dopamine uptake (-76%). Preincubation with dopamine (100 microM) caused a 60% inhibition of subsequent [3H]dopamine uptake. This dopamine-induced inhibition was attenuated by diethylenetriaminepentaacetic acid (1 mM), which can prevent iron-catalyzed oxidation of dopamine during the preincubation, but was unaffected by the monoamine oxidase inhibitor pargyline (10 microM). None of these incubations caused a loss of membrane integrity as indicated by lactate dehydrogenase release. These findings suggest that reactive oxygen species and possibly dopamine quinones can modify dopamine transport function.
S B Berman; M J Zigmond; T G Hastings
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  67     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-09-19     Completed Date:  1996-09-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  593-600     Citation Subset:  IM    
Department of Neuroscience, University of Pittsburgh, Pennsylvania 15260, USA.
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MeSH Terms
Antioxidants / pharmacology
Ascorbic Acid / pharmacology
Biological Transport / drug effects
Carrier Proteins / metabolism*
Cell Membrane Permeability / drug effects
Chelating Agents / pharmacology
Corpus Striatum / metabolism
Dopamine / metabolism*
Dopamine Plasma Membrane Transport Proteins
Glutathione / pharmacology
L-Lactate Dehydrogenase / metabolism
Membrane Glycoproteins*
Membrane Transport Proteins*
Nerve Tissue Proteins*
Pentetic Acid / pharmacology
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism*
Synaptosomes / metabolism
Xanthine Oxidase / metabolism
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Carrier Proteins; 0/Chelating Agents; 0/Dopamine Plasma Membrane Transport Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/Reactive Oxygen Species; 50-81-7/Ascorbic Acid; 67-43-6/Pentetic Acid; 70-18-8/Glutathione; EC Dehydrogenase; EC Oxidase

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