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

Mol Cell Biol Res Commun. 2000 Aug;4(2):90-7. doi: 10.1006/mcbr.2000.0264.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / toxicity*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • ATP-Binding Cassette Transporters*
  • Animals
  • Biotransformation
  • Blotting, Western
  • Carcinogens / toxicity*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Down-Regulation
  • Endotoxins / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Abcc2 protein, rat
  • Carcinogens
  • Carrier Proteins
  • Endotoxins
  • RNA, Messenger
  • 2-Acetylaminofluorene