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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2002-6-10
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pubmed:abstractText |
The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). Upon binding to this site, Zn2+ causes inhibition of [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) uptake. We investigated the effect of Zn2+ on outward transport by superfusing hDAT-expressing HEK-293 cells preloaded with [3H]MPP+. Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET). Mutation of the Zn2+ coordinating residue His(193) to Lys (the corresponding residue in hNET) eliminated the effect of Zn2+ on efflux. Conversely, the reciprocal mutation (K189H) conferred Zn2+ sensitivity to hNET. The intracellular [3H]MPP+ concentration was varied to generate saturation isotherms; these showed that Zn2+ increased V(max) for efflux (rather than K(M-Efflux-intracellular)). Thus, blockage of inward transport by Zn2+ is not due to a simple inhibition of the transporter turnover rate. The observations provide evidence against the model of facilitated exchange-diffusion and support the concept that inward and outward transport represent discrete operational modes of the transporter. In addition, they indicate a physiological role of Zn2+, because Zn2+ also facilitated transport reversal of DAT in rat striatal slices.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amphetamines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Ions,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Biogenic Amine Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21505-13
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11940571-Amphetamines,
pubmed-meshheading:11940571-Animals,
pubmed-meshheading:11940571-Binding Sites,
pubmed-meshheading:11940571-Biological Transport,
pubmed-meshheading:11940571-Cell Line,
pubmed-meshheading:11940571-DNA, Complementary,
pubmed-meshheading:11940571-Dopamine,
pubmed-meshheading:11940571-Dose-Response Relationship, Drug,
pubmed-meshheading:11940571-Female,
pubmed-meshheading:11940571-Humans,
pubmed-meshheading:11940571-Ions,
pubmed-meshheading:11940571-Kinetics,
pubmed-meshheading:11940571-Membrane Glycoproteins,
pubmed-meshheading:11940571-Membrane Transport Proteins,
pubmed-meshheading:11940571-Mutation,
pubmed-meshheading:11940571-Neuropeptides,
pubmed-meshheading:11940571-Norepinephrine,
pubmed-meshheading:11940571-Potassium,
pubmed-meshheading:11940571-Rats,
pubmed-meshheading:11940571-Rats, Sprague-Dawley,
pubmed-meshheading:11940571-Temperature,
pubmed-meshheading:11940571-Time Factors,
pubmed-meshheading:11940571-Transfection,
pubmed-meshheading:11940571-Vesicular Biogenic Amine Transport Proteins,
pubmed-meshheading:11940571-Zinc
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pubmed:year |
2002
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pubmed:articleTitle |
The role of zinc ions in reverse transport mediated by monoamine transporters.
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pubmed:affiliation |
Institute of Pharmacology, University of Vienna, Währingerstrasse 13a, A-1090 Vienna, Austria.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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