MDR1 P-glycoprotein Is a Lipid Translocase of Broad Specificity, While MDR3 P-glycoprotein Specifically Translocates Phosphatidylcholine

Cell. 1996 Nov 1;87(3):507-17. doi: 10.1016/s0092-8674(00)81370-7.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • ATP-Binding Cassette Transporters / physiology*
  • Animals
  • Biological Transport, Active / drug effects
  • Cell Line
  • Cell Polarity
  • Epithelium
  • Humans
  • Kidney
  • Lipid Metabolism*
  • Lipids / chemistry
  • Lipids / classification
  • Mice
  • Phosphatidylcholines / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • Swine
  • Transfection
  • Verapamil / pharmacology
  • Vincristine / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Lipids
  • Phosphatidylcholines
  • Recombinant Fusion Proteins
  • Vincristine
  • multidrug resistance protein 3
  • Verapamil