Abstract
Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-4-phenylpyridinium / antagonists & inhibitors
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1-Methyl-4-phenylpyridinium / metabolism*
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1-Methyl-4-phenylpyridinium / toxicity
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Adrenal Glands / chemistry
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Amines / metabolism
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Amino Acid Sequence
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Animals
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Base Sequence
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Biological Transport / genetics
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Brain Chemistry
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CHO Cells
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Cloning, Molecular
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Cricetinae
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DNA / physiology*
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Inactivation, Metabolic
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Models, Molecular
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Molecular Sequence Data
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Rats
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Sequence Alignment
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Vesicular Monoamine Transport Proteins
Substances
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Amines
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Slc18a1 protein, rat
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Slc18a2 protein, rat
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Vesicular Monoamine Transport Proteins
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DNA
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1-Methyl-4-phenylpyridinium
Associated data
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GENBANK/L05499
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GENBANK/M87278
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GENBANK/M94264
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GENBANK/M97380
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GENBANK/M97381
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GENBANK/S72766
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GENBANK/S72767
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GENBANK/S72768
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GENBANK/S72769
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GENBANK/S72771