Abstract

OBJECTIVE: The purpose of this study was to characterize the mechanisms involved in the placental clearance of hypoxanthine. STUDY DESIGN: Uptake of isotope-labeled compounds was measured in the in situ perfused guinea pig placenta and in membrane vesicles isolated from the human syncytiotrophoblast. RESULTS: In the guinea pig hypoxanthine uptake (from the fetal circulation) proceeded by a saturable (Michaelis constant approximately 90 mumol/L), sodium-dependent mechanism that was inhibited by 19 mmol/L papaverine but not by 10 mumol/L nitrobenzylthioinosine or 10 mmol/L uridine. Uridine uptake was blocked by nitrobenzylthioinosine but not by papaverine or 4 mmol/L hypoxanthine. In human brush-border (maternal-facing) membrane vesicles hypoxanthine influx was sodium independent and best fitted to a saturable (Michaelis constant 290 +/- 45 mumol/L) plus a linear component. Saturable influx was blocked by papaverine but not by nitrobenzylthioinosine. Uridine uptake was not affected by 4 mmol/L hypoxanthine. Mediated hypoxanthine uptake by human basal (fetal-facing) membrane vesicles was not detected. CONCLUSION: At both placental blood-tissue interfaces hypoxanthine transport occurs through specific mechanisms that are different from the nucleoside transporters.