Abstract
The human MDR1 P-glycoprotein (Pgp) extrudes a variety of drugs across the plasma membrane. The homologous MDR3 Pgp is required for phosphatidylcholine secretion into bile. After stable transfection of epithelial LLC-PK1 cells, MDR1 and MDR3 Pgp were localized in the apical membrane. At 15 degrees C, newly synthesized short-chain analogs of various membrane lipids were recovered in the apical albumin-containing medium of MDR1 cells but not control cells. MDR inhibitors and energy depletion reduced apical release. MDR3 cells exclusively released a short-chain phosphatidylcholine. Since no vesicular secretion occurs at 15 degrees C, the short-chain lipids must have been translocated by the Pgps across the plasma membrane before extraction into the medium by the lipid-acceptor albumin.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
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ATP-Binding Cassette Transporters / physiology*
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Animals
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Biological Transport, Active / drug effects
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Cell Line
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Cell Polarity
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Epithelium
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Humans
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Kidney
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Lipid Metabolism*
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Lipids / chemistry
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Lipids / classification
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Mice
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Phosphatidylcholines / metabolism*
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Recombinant Fusion Proteins / metabolism
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Substrate Specificity
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Swine
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Transfection
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Verapamil / pharmacology
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Vincristine / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP-Binding Cassette Transporters
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Lipids
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Phosphatidylcholines
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Recombinant Fusion Proteins
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Vincristine
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multidrug resistance protein 3
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Verapamil