FOLATE TRANSPORT PROTEINS MEDIATE THE BIDIRECTIONAL TRANSPORT OF 5-METHYLTETRAHYDROFOLATE IN CULTURED HUMAN PROXIMAL TUBULE CELLS

Although reabsorption across the apical (AP) membrane of the renal pro ximal tubule cell plays a vital role in the conservation of plasma 5-m ethyltetrahydrofolate, basolateral (BL) membrane-directed secretory pa thways may also be important in regulating the urinary excretion of fo late. Folate transport proteins, folate receptor and the reduced folat e carrier have been implicated in the renal conservation of folate acr oss the AP membrane, but their role in BL membrane-directed folate tra nsport has not been studied. 5-Methyltetrahydrofolate transport across the AP and BL membranes of human proximal tubule cells was studied in cells grown on membrane inserts to allow optimum differentiation of A P and BL domains. Colchicine, an inhibitor of vesicular-mediated endoc ytosis, inhibited AP binding and AP-directed transport without affecti ng BL transport. Probenecid, an inhibitor of anion exchange, did not a ffect binding, but inhibited both AP and BL-directed transport with a greater effect on BL transport. Folio acid abolished AP binding of 5-m ethyltetrahydrofolate, but diminished AP-mediated transport by only 50 %. These data suggest that both the folate receptor and the reduced fo late carrier participate in AP uptake of folates by human kidney cells , but that BL-mediated uptake occurs primarily by the reduced folate c arrier. Folate transport from the secretory direction occurred as read ily as that from the reabsorptive direction, indicating that altered s ecretion could mediate excess urinary folate excretion.