Excretion of foetal bilirubin by the rat placenta-maternal liver tandem.
Using plasma membrane vesicles from human trophoblast, carrier-mediated transport of unconjugated bilirubin (UCBR) has been reported. In the present work, using the in situ perfused rat placenta-maternal liver tandem, the relevance of this pathway in vivo was investigated. After single-pass perfusion of rat placenta through the umbilical artery with 0.25 micromol [(3)H]-UCBR, approximately 15 per cent of it was taken up by the placenta, detected in maternal serum (>96 per cent was unconjugated) and subsequently secreted into maternal bile (approximately 15 per cent of administered dose; >88 per cent was glucuronidated bilirubin). Co-administration through the umbilical artery of 0.25 micromol [(3)H]-UCBR and 2.5 micromol unlabelled UCBR, bromosulfophthalein, cholic acid or biliverdin IXalpha, reduced [(3)H]-UCBR placenta uptake, and the amount of radioactivity found in the maternal serum and bile. Co-administration into maternal jugular vein of 0.1 micromol [(3)H]-UCBR-a dose 3-fold higher than that reaching the maternal compartment in placenta perfusion experiments-and 1.0 micromol bromosulfophthalein, cholic acid or biliverdin IXalpha, resulted in no marked inhibition of the amount of radioactivity bile output. When antipyrine and [(3)H]-UCBR were continuously co-infused to the mother, similar antipyrine concentrations in maternal and foetal serum were reached in approximately 15 min, while progressive increase in [(3)H]-bilirubin concentrations in maternal serum above 70 microM was accompanied by a very low transfer of this compound into foetal compartment where [(3)H]-bilirubin concentrations were always <10 microM. These results suggest that the transfer of UCBR across the rat placenta occurs, without biotransformation, via a foetal-to-maternal mainly unidirectional pathway that can be cis-inhibited by UCBR and other cholephilic organic anions.
Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain.
O
O
Briz
R I R
RI
Macias
M A
MA
Serrano
J
J
González-Gallego
J E
JE
Bayón
J J G
JJ
Marin
D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D001663:Bilirubin / Q000378:metabolism* / Q000493:pharmacokinetics; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014327:Trophoblasts / Q000378:metabolism*
D001663:Bilirubin; D000983:Antipyrine