Transport of folates at maternal and fetal sides of the placenta: lack of inhibition by methotrexate.
Folate (pteroylglutamate) and methotrexate rapid (seconds) uptake by the trophoblast was investigated from either the maternal or fetal circulations of the isolated dually-perfused guinea-pig placenta. Tissue uptake was measured by using a single-circulation paired-tracer (3H-test and 14C-extracellular marker) technique. [3H]Folate uptakes were 80 and 52% (mean) in perfusates without unlabelled folate, on maternal and fetal sides, respectively. There was negligible 3H-tracer backflux into the circulation up to 6 min probably due to metabolic sequestration. [3H]Methotrexate uptakes were about 85 and 22% on maternal and fetal sides, respectively; however these uptakes were followed by rapid and complete backflux of the label. Specific transplacental transfer of [3H]folate or [3H]methotrexate in either direction was not detectable within 5-6 min. At the brush-border side (maternal) uptake of [3H]folate was highly inhibited by 100 nM unlabelled folate or its reduced form, methyltetrahydrofolate (the main form in plasma); however, equimolar methotrexate (an antifolate chemotherapeutic agent) failed to produce any inhibition of folate uptake. Our findings demonstrate that on both sides of the placenta a high-affinity transport system exists for trophoblast uptake of folate compounds. For methotrexate, either a separate transport system may exist or methotrexate may have a very low affinity for the folate system. These results are distinct from the findings reported in mouse L1210 leukemia cells.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D006168:Guinea Pigs; D007700:Kinetics; D008727:Methotrexate / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D014316:Tritium; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D002250:Carbon Radioisotopes; D014316:Tritium; D005492:Folic Acid; D008727:Methotrexate