title: P-glycoprotein-mediated renal tubular secretion of digoxin: the toxicological significance of the urine-blood barrier model.
abstract: We provide direct evidence that verapamil inhibits active digoxin secretion in renal tubular cells (LLC-PK1), and that verapamil increases cellular accumulation of digoxin. These findings suggest that verapamil inhibits the digoxin active secretory transport at the apical membranes, supporting the theory that P-glycoprotein mediates digoxin secretion in the renal tubular cells. Based on existing data on digoxin transport, we present a hypothetical model for the renal handling of digoxin, implying that P-glycoprotein functions as a driving mechanism of a unidirectional "urine-blood" barrier.
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: C
authors.initials: C
authors.lastname: Woodland
authors.forename: P A
authors.initials: PA
authors.lastname: Harper
authors.forename: G
authors.initials: G
authors.lastname: Koren
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002460:Cell Line; D004077:Digoxin / Q000493:pharmacokinetics*; D007684:Kidney Tubules / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D004077:Digoxin; D014700:Verapamil