The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi

Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H, Biber J, Forster IC. The Na+-P-i cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary P-i. Am J Physiol Renal Physiol 296: F691-F699, 2009. First published December 10, 2008; doi:10.1152/ajprenal.90623.2008.-The principal mediators of renal phosphate (P-i) reabsorption are the SLC34 family proteins NaPi-IIa and NaPi-IIc, localized to the proximal tubule (PT) apical membrane. Their abundance is regulated by circulatory factors and dietary P-i. Although their physiological importance has been confirmed in knockout animal studies, significant P-i reabsorptive capacity remains, which suggests the involvement of other secondary-active P-i transporters along the nephron. Here we show that a member of the SLC20 gene family (PiT-2) is localized to the brush-border membrane (BBM) of the PT epithelia and that its abundance, confirmed by Western blot and immunohistochemistry of rat kidney slices, is regulated by dietary P-i. In rats treated chronically on a high-P-i (1.2%) diet, there was a marked decrease in the apparent abundance of PiT-2 protein in kidney slices compared with those from rats kept on a chronic low-P-i (0.1%) diet. In Western blots of BBM from rats that were switched from a chronic low-to high-P-i diet, NaPi-IIa showed rapid downregulation after 2 h; PiT-2 was also significantly down-regulated at 24 h and NaPi-IIc after 48 h. For the converse dietary regime, NaPi-IIa showed adaptation within 8 h, whereas PiT-2 and NaPi-IIc showed a slower adaptive trend. Our findings suggest that PiT-2, until now considered as a ubiquitously expressed P-i housekeeping transporter, is a novel mediator of P-i reabsorption in the PT under conditions of acute P-i deprivation, but with a different adaptive time course from NaPi-IIa and NaPi-IIc.