Fetal excretion of the fluorescent bile acid derivative cholylglycylamido-fluorescein (FITC-GC) by the rat placenta maternal liver tandem

Bile acid transfer from the fetus to maternal bile was studied using in situ perfused rat placenta on day 21 of gestation and a fluorescent derivative of glycocholate (GC): cholylglycylamido-fluorescein (FITC-GC). Single-pass perfusion of the placenta with 0.25 mu mol FITC-GC via the umbilical artery over 5 min was followed by the output of 6 per cent of this amount in maternal bile collected over the ensuing 120 min. This amount was reduced (-35 per cent) by simultaneous administration of 2.5 mu mol GC through the jugular vein of the mother. This inhibition was stronger (-73 per cent) when 2.5 mu mol GC was co-infused with FITC-GC through the umbilical artery. These results suggested that FITC-GC was, at least in part, transported by bile acid carriers across both the liver and the placenta. Using isolated perfused rat livers obtained from female virgin or 21-day pregnant rats, a slight increase in the residence time of FITC-GC in the liver of pregnant rats was found. However, no change in the ability of the liver to take up FITC-GC was observed. By contrast, when FITC-GC was injected into the left jugular vein of anaesthetized pregnant rats, a delayed plasma disappearance of this compound was seen, which may have been due in part to the existence of a transient and reversible FITC-GC exchange with the placental-fetal compartment. The maximal rate of FITC-GC output into bile after FITC-GC administration (1 mu mol/100 g body weight) to pregnant rats was approximately 0.2 mu mol/min, while maximal FITC-GC bile output was approximately 1 nmol/min when this compound was given through the umbilical artery (2.5 mu mol). Therefore, the rate of FITC-GC output into bile was considered to reflect the rate of transfer across the placenta. Using this approach no saturation but rather a linear regression (slope=1.1 mu l/min, p<0.05) was found between placental transfer and placental perfusate concentrations in the 10-1000-mu mol/l FITC-GC range. In summary, the in situ perfused rat placenta is a useful model to study the fetal excretion of cholephilic compounds, and transfer across the trophoblast would be the limiting step in the excretion of fetal bile acids by the placenta-maternal liver tandem. (C) 1998 W. B. Saunders Company Ltd.