Factors affecting the expression and function of P-glycoprotein in rats: drug treatments and diseased states.
The expression and function of P-glycoprotein (P-gp), an ATP-dependent efflux pump, were examined in rats pretreated with dexamethasone (DEX), an inducer of P-gp, and in rats with glycerol-induced acute renal failure (ARF) and with CCl4-induced acute hepatic failure (AHF). DEX pretreatment increased the P-gp level and its functional activity in the intestine. In contrast, in ARF and AHF rats, the in vivo P-gp function was systemically suppressed, even though the level of P-gp remained unchanged or rather increased. In Caco-2 cells, the plasma collected from diseased rats exhibited a greater inhibitory effect on P-gp function than did plasma from control rats. A higher-plasma level of corticosterone, an endogenous P-gp substrate/inhibitor, was observed in the disease rats. These findings indicate that the actual in vivo function of P-gp cannot be predicted merely from the expression level of P-gp, and suggest that some endogenous P-gp-related compounds such as corticosterone participate in the regulation of in vivo P-gp function in diseased states.
Murakami
T
T
Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University, Hiroshima, Japan.
Yumoto
R
R
Nagai
J
J
Takano
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D004194:Disease; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism; D051381:Rats
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1