Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy.
The expression of hepatic multidrug resistance-associated protein (Mrp)1, 2, 3, and 6 and organic anion transporting polypeptides (Oatp)1 and 2 were examined in control and 20- to 21-day pregnant rats. Western analysis showed that expression of Oatp2 was decreased 50% in pregnancy, whereas expression of Oatp1 did not change. Expression of Mrp2 protein determined by Western analysis of total liver homogenate decreased to 50% of control levels in pregnant rats, consistent with studies using plasma membranes. Confocal immunohistochemistry showed that Mrp2 expression was confined to the canalicular membrane in both control and pregnant rats and was not detectable in intracellular compartments. In isolated perfused liver, the biliary excretion of 2,4-dintrophenyl-glutathione was significantly decreased in pregnancy, consistent with decreased expression of Mrp2. The expression of the basolateral transporter Mrp1 was not altered in pregnancy, whereas expression of Mrp6 mRNA was decreased by 60%. Expression of Mrp3 was also decreased by 50% in pregnant rat liver, indicating differential regulation of Mrp isoforms in pregnancy. These data also demonstrate that decreased Mrp2 expression is not necessarily accompanied by increased Mrp3 expression.
Cao
Jingsong
J
Graduate Center for Toxicology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536 - 0305, USA.
Stieger
Bruno
B
Meier
Peter J
PJ
Vore
Mary
M
D000818:Animals; D001692:Biological Transport; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D024101:Mitochondrial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012269:Ribosomal Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014018:Tissue Distribution
D005978:Glutathione; D024101:Mitochondrial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C093947:MRP2 protein, S cerevisiae; C114462:multidrug resistance-associated protein 3; C030190:S-(2,4-dinitrophenyl)glutathione