|Dopamine transporter expression confers cytotoxicity to low doses of the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium.|
|PMID: 8410185 Owner: NLM Status: MEDLINE|
|The uptake of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was studied in various mammalian cell lines transfected, respectively, with the cloned human and rat dopamine transporters, and compared with rat striatal synaptosome preparations. Only in neuronally derived cell lines such as NG108-15, NS20Y, and SK-N-MC cells did MPP+ have a KM for the cloned transporters comparable to that of dopamine as seen in rat striatal synaptosomes. In non-neuronally derived cells such as COS-7, CHO, and Ltk- cells transiently or permanently expressing the transporters, the KM of MPP+ was at least 10-fold higher. The permanent expression of either the cloned human or rat dopamine transporters conferred to SK-N-MC cells susceptibility to the cytotoxic effects of low concentrations of MPP+. The extent of this effect was dependent on the expression level of the dopamine transporters and could be specifically antagonized by the catecholamine uptake inhibitor mazindol. There were no significant differences in the susceptibility to MPP+ of cells expressing similar levels of either the human or rat dopamine transporter. The demonstration for the first time of a quantitative relationship between the cellular expression of the plasma membrane transporter and the extent of the cytotoxic effects of MPP+ suggests that known differences in vulnerability of various brain regions to MPP+ cytotoxicity might be related to their actual content of dopamine uptake sites.(ABSTRACT TRUNCATED AT 250 WORDS)|
|C Pifl; B Giros; M G Caron|
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|Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.|
|Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 13 ISSN: 0270-6474 ISO Abbreviation: J. Neurosci. Publication Date: 1993 Oct|
|Created Date: 1993-11-12 Completed Date: 1993-11-12 Revised Date: 2007-11-14|
Medline Journal Info:
|Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: UNITED STATES|
|Languages: eng Pagination: 4246-53 Citation Subset: IM|
|Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.|
|APA/MLA Format Download EndNote Download BibTex|
Biological Transport / drug effects
Carrier Proteins / biosynthesis*
Cell Survival / drug effects
Dopamine / metabolism*
Dopamine Plasma Membrane Transport Proteins
Membrane Transport Proteins*
Molecular Sequence Data
Nerve Tissue Proteins*
Neurotoxins / metabolism, toxicity*
Parkinson Disease, Secondary / chemically induced
Synaptosomes / metabolism
Tumor Cells, Cultured
|1P-53-NIH 44221//PHS HHS; MH-40159/MH/NIMH NIH HHS; NS-15976/NS/NINDS NIH HHS|
|0/Carrier Proteins; 0/DNA Primers; 0/Dopamine Plasma Membrane Transport Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/Neurotoxins; 48134-75-4/1-Methyl-4-phenylpyridinium|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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