Internalization and apical-to-basolateral transport of folate in rat kidney proximal tubule

Folate derivatives are filtered in the glomeruli and reabsorbed within the nephron. The amount filtered largely exceeds the minimum daily requirements. Thus folate reabsorbed within the kidney must be returned to the circulation. To establish whether renal proximal tubule can accomplish this by transport of [H-3]folate across the cell, microperfusion of rabbit proximal tubule with [H-3]folate and [C-14]inulin was performed. Transtubular transport of [H-3]folate was 5 +/- 1% (0.25 +/- 0.07 fmol/min) of perfused amount/mm tubule and remained constant during a 2-h perfusion period. An accumulation of 15 +/- 4% (0.8 +/- 0.3 fmol/min) of perfused amount/mm tubule was observed during the same period. Furthermore, to determine whether endocytosis may be involved in the initial process of folate uptake in proximal tubule cells, we performed light microscopy autoradiography on cryosections of rat kidney cortex incubated with [H-3]folate. Folate binding sites were located apically as well as intracellularly similar to the location of [H-3]folate when injected into the abdominal aorta and visualized by light microscopy autoradiography. Thus folate binding sites as well as internalized folate is localized both apically and intracellularly. Micropuncture of rat proximal tubules with folate-coupled collodial gold particles showed significantly increased endocytosis of folate gold when evaluated quantitatively and compared with controls injected with noncoupled gold particles (0.22 +/- 0.08 vs. 0.03 +/- 0.01 gold particles/mu m(2) tubule cell). The results show that kidney proximal tubule cells are capable of transcellular transport of [H-3]folate with limited capacity. Folate gold particle uptake suggests that folate can be internalized by endocytosis.