Mechanisms for the transport of unconjugated bilirubin in human trophoblastic BeWo cells.
To evaluate mechanisms that mediate passage of unconjugated bilirubin (UCB) across placenta, the transport of [3H]UCB was studied in the human trophoblastic, BeWo cell line. When plotted against the unbound UCB concentration [Bf], uptake exhibited saturative kinetics with a similar apparent Km ( approximately 30 nM) for BeWo cells grown either in polarized (Transwell) or non-polarized fashion (dish). UCB release from cells, but not uptake, was inhibited by sulfobromophthalein but not by taurocholate, and almost abolished by MK571, a specific inhibitor of the activity of multidrug resistance-associated proteins (MRPs). MRP1 and MRP5 were both present in BeWo cells and the expression of MRP1, but not MRP5, was markedly higher in polarized cells. These data indicate that UCB is taken up from the fetal circulation by a still undefined, saturative process not shared by other organic anions and is then excreted to maternal circulation by proteins of the MRP family.
Pascolo
L
L
CSF-Department of BBCM, University of Trieste, Via Giorgeri 1, 34127 Trieste, Italy.
Fernetti
C
C
Garcia-Mediavilla
M V
MV
Ostrow
J D
JD
Tiribelli
C
C
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D016764:Cell Polarity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004058:Diffusion; D005260:Female; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013448:Sulfobromophthalein / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D014316:Tritium; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D001663:Bilirubin; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D011422:Propionates; D011804:Quinolines; D012333:RNA, Messenger; D013448:Sulfobromophthalein; D013656:Taurocholic Acid; D014316:Tritium; C120809:ABCC5 protein, human; C078444:MSH3 protein, human; C059141:verlukast; C421109:multidrug resistance-associated protein 1