Morshed K M, Ross D M, McMartin K E
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130, USA.
J Nutr. 1997 Jun;127(6):1137-47. doi: 10.1093/jn/127.6.1137.
Although reabsorption across the apical (AP) membrane of the renal proximal tubule cell plays a vital role in the conservation of plasma 5-methyltetrahydrofolate, basolateral (BL) membrane-directed secretory pathways may also be important in regulating the urinary excretion of folate. Folate transport proteins, folate receptor and the reduced folate carrier have been implicated in the renal conservation of folate across the AP membrane, but their role in BL membrane-directed folate transport 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 AP and BL domains. Colchicine, an inhibitor of vesicular-mediated endocytosis, inhibited AP binding and AP-directed transport without affecting BL transport. Probenecid, an inhibitor of anion exchange, did not affect binding, but inhibited both AP and BL-directed transport with a greater effect on BL transport. Folic acid abolished AP binding of 5-methyltetrahydrofolate, but diminished AP-mediated transport by only 50%. These data suggest that both the folate receptor and the reduced folate carrier participate in AP uptake of folates by human kidney cells, but that BL-mediated uptake occurs primarily by the reduced folate carrier. Folate transport from the secretory direction occurred as readily as that from the reabsorptive direction, indicating that altered secretion could mediate excess urinary folate excretion.
尽管肾近端小管细胞顶端（AP）膜的重吸收在血浆5-甲基四氢叶酸的保存中起着至关重要的作用，但基底外侧（BL）膜导向的分泌途径在调节叶酸的尿排泄中可能也很重要。叶酸转运蛋白、叶酸受体和还原型叶酸载体与肾通过AP膜保存叶酸有关，但它们在BL膜导向的叶酸转运中的作用尚未得到研究。在生长于膜插入物上的细胞中研究了5-甲基四氢叶酸在人近端小管细胞AP和BL膜上的转运，以实现AP和BL结构域的最佳分化。秋水仙碱是一种囊泡介导的内吞作用抑制剂，它抑制AP结合和AP导向的转运，但不影响BL转运。丙磺舒是一种阴离子交换抑制剂，它不影响结合，但抑制AP和BL导向的转运，对BL转运的影响更大。叶酸消除了5-甲基四氢叶酸的AP结合，但仅使AP介导的转运减少50%。这些数据表明，叶酸受体和还原型叶酸载体都参与人肾细胞对叶酸的AP摄取，但BL介导的摄取主要通过还原型叶酸载体发生。叶酸从分泌方向的转运与从重吸收方向的转运一样容易，这表明分泌改变可能介导过量的尿叶酸排泄。
