FOLATE TRANSPORT PATHWAYS REGULATE URINARY-EXCRETION OF 5-METHYLTETRAHYDROFOLATE IN ISOLATED-PERFUSED RAT-KIDNEY

The reabsorption of 5-methyltetrahydrofolic acid (5-CH3-H(4)PteGlu) by the renal proximal tubule has an important role in the maintenance of plasma folate concentrations. However, the mechanism by which this vi tamin traverses the renal epithelium remains to be determined. Studies in cultured cells have suggested that the folate receptor in associat ion with a probenecid-sensitive anion carrier may be involved in the t ransmembrane transport of the vitamin. Because 5-CH3-H(4)PteGlu is rea bsorbed and metabolized in the isolated perfused rat kidney (IPRK) in a similar manner to in vivo models, the IPRK was used to evaluate path ways involved in folate reabsorption. Reabsorption of 5-CH3-H(4)PteGlu could not be saturated in the isolated perfused rat kidney, even at c oncentrations up to 2 mu mol/L. Folic acid (PteGlu) was used as a comp etitive inhibitor of FR-dependent reabsorption of 5-CH3-H(4)PteGlu. Wh en 5-CH3-H(4)PteGlu was maintained at 1 nmol/L (a concentration at whi ch receptor-mediated transport should be maximal), PteGlu (up to 100 n mol/L) had no effect on reabsorption. The addition of probenecid (1 mm ol/L) did not affect the reabsorption of 5-CH3-H(4)PteGlu but inhibite d the fractional excretion of the anion para-aminohippurate. Probeneci d also inhibited the urinary excretion of 5-CH3-H(4)PteGlu metabolites , indicating that reabsorbed 5-CH3-H(4)PteGlu was metabolized to produ cts that were subsequently secreted into the urine by anion exchange p athways. The physiological importance of a folate receptor-mediated re absorption of 5-CH3-H(4)PteGlu appears to be minor in the isolated per fused rat kidney, whereas nonspecific pathways appear to play a major role in the renal folate reabsorption.