P-glycoprotein-mediated transcellular transport of MDR-reversing agents

FEBS Lett. 1993 Jun 7;324(1):99-102. doi: 10.1016/0014-5793(93)81540-g.

Abstract

Understanding of the interactions between P-glycoprotein and multidrug resistance (MDR) reversing agents is important in designing more effective MDR modulators. We examined transcellular transport of several MDR modulators by using a drug-sensitive epithelial cell line, LLC-PK1, and its transformant cell line, LLC-GA5-COL300, which expresses human P-glycoprotein on the apical surface. Basal-to-apical transports of azidopine and diltiazem across the LLC-GA5-COL300 monolayer were increased and apical-to-basal transports were decreased compared to those across the LLC-PK1 monolayer, indicating that P-glycoprotein transports azidopine and diltiazem. Movements of nitrendipine and staurosporine across the epithelial monolayer were not affected by P-glycoprotein. These results suggests that some MDR modulators exert their inhibitory effect not only by blocking the initial binding of anticancer drugs but throughout the course of the transport process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Alkaloids / metabolism*
  • Animals
  • Azides / metabolism*
  • Biological Transport
  • Carbon Radioisotopes
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Line, Transformed
  • Dihydropyridines / metabolism*
  • Diltiazem / metabolism*
  • Drug Resistance*
  • Epithelium / metabolism
  • Humans
  • Kinetics
  • Membrane Glycoproteins / metabolism*
  • Nitrendipine / metabolism*
  • Protein Kinase C / antagonists & inhibitors
  • Staurosporine
  • Sucrose / metabolism
  • Transfection
  • Tritium

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Alkaloids
  • Azides
  • Carbon Radioisotopes
  • Carrier Proteins
  • Dihydropyridines
  • Membrane Glycoproteins
  • Tritium
  • Sucrose
  • azidopine
  • Nitrendipine
  • Protein Kinase C
  • Diltiazem
  • Staurosporine