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 re quirements. Thus folate reabsorbed within the kidney must be returned to the circulation. To establish whether renal proximal tubule can acc omplish this by transport of [H-3]folate across the cell, microperfusi on of rabbit proximal tubule with [H-3]folate and [C-14]inulin was per formed. Transtubular transport of [H-3]folate was 5 +/- 1% (0.25 +/- 0 .07 fmol/min) of perfused amount/mm tubule and remained constant durin g a 2-h perfusion period. An accumulation of 15 +/- 4% (0.8 +/- 0.3 fm ol/min) of perfused amount/mm tubule was observed during the same peri od. Furthermore, to determine whether endocytosis may be involved in t he initial process of folate uptake in proximal tubule cells, we perfo rmed light microscopy autoradiography on cryosections of rat kidney co rtex incubated with [H-3]folate. Folate binding sites were located api cally as well as intracellularly similar to the location of [H-3]folat e when injected into the abdominal aorta and visualized by light micro scopy autoradiography. Thus folate binding sites as well as internaliz ed folate is localized both apically and intracellularly. Micropunctur e of rat proximal tubules with folate-coupled collodial gold particles showed significantly increased endocytosis of folate gold when evalua ted 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 capaci ty. Folate gold particle uptake suggests that folate can be internaliz ed by endocytosis.