Evidence for a multidrug resistance-associated protein 1 (MRP1)-related transport system in cultured rat liver biliary epithelial cells

Life Sci. 1999;64(9):763-74. doi: 10.1016/s0024-3205(98)00618-3.

Abstract

Cellular accumulation and efflux of the anionic fluorescent dye carboxy-2',7'-dichlorofluorescein (CF) were studied in rat liver SDVI cells thought to derive from primitive bile ductules, in order to characterize carrier-related membrane transport of organic anions in epithelial cells. Probenecid, a common blocker of anion transport, was found to strongly enhance CF levels in SDVI cells in a dose-dependent manner through inhibition of dye efflux. Such an outwardly-directed transport was demonstrated to be temperature-dependent and down-regulated by various metabolic inhibitors, therefore outlining its requirement for energy; it was shown to be Na+- and membrane potential-independent and inhibited by anionic drugs such as indomethacin, indoprofen and rifamycin B. These functional features are closed to those described for multidrug resistance-associated protein 1 (MRP1) that was furthermore demonstrated, in contrast to P-glycoprotein, to be expressed in SDVI cells and to lower CF accumulation in MRP1-overexpressing drug-resistant tumor cells. These data therefore suggest that active membrane transport of organic anions such as CF occurs in epithelial cells like cultured liver biliary SDVI cells through a MRP1-related efflux system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Animals, Newborn
  • Bile Ducts, Intrahepatic / cytology
  • Bile Ducts, Intrahepatic / drug effects
  • Bile Ducts, Intrahepatic / metabolism*
  • Biological Transport
  • Blotting, Northern
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Fluoresceins / metabolism
  • Indomethacin / pharmacology
  • Indoprofen / pharmacology
  • Multidrug Resistance-Associated Proteins
  • Probenecid / pharmacology
  • RNA / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Rifamycins / pharmacology
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Fluoresceins
  • Multidrug Resistance-Associated Proteins
  • Rifamycins
  • 5(6)-carboxy-2',7'-dichlorofluorescein
  • RNA
  • rifamycin B
  • Indoprofen
  • Probenecid
  • Indomethacin