title: P-glycoprotein-mediated transcellular transport of MDR-reversing agents.
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.
authors.affiliation: Department of Agricultural Chemistry, Faculty of Agriculture, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saeki
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: R
authors.initials: R
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Komano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000378:metabolism*; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D004095:Dihydropyridines / Q000378:metabolism*; D004110:Diltiazem / Q000378:metabolism*; D004351:Drug Resistance; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine; D013395:Sucrose / Q000378:metabolism; D014162:Transfection; D014316:Tritium
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D001386:Azides; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D004095:Dihydropyridines; D008562:Membrane Glycoproteins; D014316:Tritium; D013395:Sucrose; C041130:azidopine; D009568:Nitrendipine; D011493:Protein Kinase C; D004110:Diltiazem; D019311:Staurosporine