Energy-dependent transport of digoxin across renal tubular cell monolayers (LLC-PK1)

Can J Physiol Pharmacol. 1993 Jan;71(1):40-7. doi: 10.1139/y93-006.

Abstract

Digoxin secretory transport across renal tubular cell monolayers (LLC-PK1) grown on permeable filters was characterized. Metabolic inhibitors reduced total and specific basolateral to apical (B-A) flux of digoxin and conversely increased the apical to basolateral (A-B) flux. The specific transport of digoxin from the basolateral to the apical compartment was saturable, with a maximum velocity of transport of 184.5 +/- 38.0 pmol.cm-2.h-1 and a Michaelis-Menten constant (Km) of 14.1 +/- 1.6 microM. In addition, B-A flux of digoxin resulted in accumulation of digoxin in the apical compartment against the concentration gradient. P-Glycoprotein inhibitors such as quinidine, verapamil, vincristine, and cyclosporine increased the net A-B flux and inhibited the total B-A flux without affecting the nonspecific flux significantly. Tetraethylammonium, a prototype substrate for an organic cation transport system, had no such effect. Our results suggest that digoxin undergoes transepithelial secretion by an energy-dependent, carrier-mediated process in renal tubules, a process that seems to be distinct from the tetraethylammonium transport system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Animals
  • Antimetabolites / pharmacology
  • Blood Proteins / metabolism
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Digoxin / pharmacokinetics*
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism*
  • Membrane Glycoproteins / metabolism
  • Swine

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antimetabolites
  • Blood Proteins
  • Carrier Proteins
  • Membrane Glycoproteins
  • Digoxin