Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure

Eur J Pharmacol. 2000 Oct 20;406(3):453-60. doi: 10.1016/s0014-2999(00)00699-3.


The effect of glycerol-induced acute renal failure on P-glycoprotein expression and function was evaluated in rats. The in vivo function of P-glycoprotein was evaluated by measuring renal secretory and biliary clearance and brain distribution of rhodamine 123 (Rho-123), a P-glycoprotein substrate, under a steady-state plasma concentration. In acute renal failure rats, the P-glycoprotein level increased 2.5-fold in the kidney, but not in the liver and brain. In contrast, P-glycoprotein function in these tissues was suppressed. Interestingly, not only the renal but also the biliary clearance of Rho-123 was correlated with the glomerular filtration rate. In Caco-2 cells, plasma from renal failure rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of Rho-123 than did plasma from control rats. In conclusion, P-glycoprotein function was systemically suppressed in acute renal failure, even though the level of P-glycoprotein remained unchanged or rather increased. This may be due to the accumulation of some endogenous P-glycoprotein substrates/modulators in the plasma in disease states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Acute Kidney Injury / metabolism*
  • Animals
  • Blotting, Western
  • Brain Chemistry
  • Caco-2 Cells
  • Cyclosporine / pharmacology
  • Glycerol
  • Humans
  • Kidney / chemistry
  • Liver / chemistry
  • Male
  • Metabolic Clearance Rate
  • Rats
  • Rats, Wistar
  • Rhodamine 123 / pharmacokinetics


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Rhodamine 123
  • Cyclosporine
  • Glycerol