Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure.
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.
Huang
Z H
ZH
Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
Murakami
T
T
Okochi
A
A
Yumoto
R
R
Nagai
J
J
Takano
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000502:physiology; D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D018938:Caco-2 Cells; D016572:Cyclosporine / Q000494:pharmacology; D005990:Glycerol; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020112:Rhodamine 123; D016572:Cyclosporine; D005990:Glycerol