Abstract
Previous studies indicate that reserpine may disrupt dopamine transporter activity. Results presented herein reveal that it also inhibits potently synaptosomal [3H]dopamine uptake. In addition, reserpine administration to rats decreased the V(max) of synaptosomal dopamine transport, as assessed ex vivo 12 h after treatment. This decrease appeared, at least in part, dissociated from concurrent inhibition of the vesicular monoamine transporter-2 (VMAT-2). In separate experiments, synaptosomal dopamine uptake did not differ between wild-type and heterozygous VMAT-2 knockout mice, and reserpine treatment did not inhibit [3H]dopamine uptake into cells heterogously expressing the human dopamine transporter. Taken together, these data suggest that reserpine may transiently alter dopamine transporter function in a noncompetitive, indirect manner.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biological Transport / drug effects
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Dopamine / pharmacokinetics
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Dopamine Plasma Membrane Transport Proteins
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Humans
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Male
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Membrane Transport Proteins / physiology*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins*
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Neuropeptides*
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Rats
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Rats, Sprague-Dawley
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Reserpine / pharmacology*
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Synaptosomes / drug effects
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Synaptosomes / metabolism
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Time Factors
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Tritium
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Tumor Cells, Cultured
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Vesicular Biogenic Amine Transport Proteins
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Vesicular Monoamine Transport Proteins
Substances
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Dopamine Plasma Membrane Transport Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Vesicular Biogenic Amine Transport Proteins
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Vesicular Monoamine Transport Proteins
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Tritium
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Reserpine
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Dopamine