Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell Biol Res Commun. 2000 Aug;4(2):90-7.

Endotoxin downregulates hepatic expression of P-glycoprotein and MRP2 in 2-acetylaminofluorene-treated rats.

Author information

1
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, M5S-2S2, Canada.

Abstract

In liver, the ATP-dependent transporters P-glycoprotein (PGP) and multidrug resistance protein-2 (MRP2) are involved in the secretion of numerous drugs and toxins in bile. Although constitutive levels of PGP and MRP-2 are decreased in rat liver after exposure to endotoxin, it is possible that induced forms of these transporters may be alternately affected. In vitro, the hepatocarcinogen, 2-acetylaminofluorene (AAF) induces expression of PGP and MRP2. Thus, we examined the influence of endotoxin on the expression of PGP and MRP2 in AAF-treated rats. Expression of PGP and MRP2 was analyzed on Westerns and by RT-PCR in livers obtained from endotoxin and control groups. In vivo, AAF treatment significantly induced PGP/mdr1 expression and imposed a significant reduction in the expression of spgp. MRP2 protein and mRNA levels were not altered by AAF administration. Endotoxin administration to both AAF-treated and non-AAF-treated rats elicited significant reductions in the protein and mRNA expression of MRP2 and PGP (P < 0.05). Our data indicate that endotoxin suppresses the overexpression of PGP and constitutive expression of MRP2 in AAF-treated rats. Furthermore, in vivo administration of AAF, which maximally induces PGP does not induce MRP2.

PMID:
11170838
DOI:
10.1006/mcbr.2000.0264
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Support Center