In vivo induction of liver P-glycoprotein expression by xenobiotics in monkeys.
P-glycoprotein (pgp), the protein product of the multidrug resistance (mdr) gene family, can confer a multidrug resistance (mdr) phenotype to cells in which it is expressed. One member of the pgp family, pgp2, is located on the hepatocyte biliary pole where it may have a role in biliary excretion. Using primates we sought to determine if mdr gene expression and pgp levels were affected by xenobiotics excreted via the bile in man. Five drugs were studied in male and female rhesus monkeys: erythromycin, rifampicin, tamoxifen, diethylstilbesterol (DES), and probenecid. For each xenobiotic, with the exception of DES, an increase in mdr2 mRNA was observed. The results suggest that expression of mdr2 is responsive to xenobiotics, or their metabolites, that require biliary excretion. We speculate that the mdr2 gene may be a member of a class of xenobiotic responsive genes coding for proteins that actively excrete xenobiotics and/or their metabolites into the bile.
Gant
T W
TW
National Cancer Institute, Bethesda, Maryland 20892, USA.
O'Connor
C K
CK
Corbitt
R
R
Thorgeirsson
U
U
Thorgeirsson
S S
SS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003720:Densitometry; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D004917:Erythromycin / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011339:Probenecid / Q000008:administration & dosage / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage / Q000633:toxicity; D013629:Tamoxifen / Q000008:administration & dosage / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D013629:Tamoxifen; D004917:Erythromycin; D004054:Diethylstilbestrol; D011339:Probenecid; D012293:Rifampin