The [Na.sup.+]-[P.sub.i] cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary [P.sub.i]

The principal mediators of renal phosphate ([P.sub.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.sub.i]. Although their physiological importance has been confirmed in knockout animal studies, significant [P.sub.i] reabsorptive capacity remains, which suggests the involvement of other secondary-active [P.sub.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.sub.i]. In rats treated chronically on a high-[P.sub.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.sub.i] (0.1%) diet. In Western blots of BBM from rats that were switched from a chronic low- to high-[P.sub.i] diet, NaPi-IIa showed rapid downregulation after 2 h; PIT-2 was also significantly downregulated 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.sub.i] housekeeping transporter, is a novel mediator of [P.sub.i] reabsorption in the PT under conditions of acute [P.sub.i] deprivation, but with a different adaptive time course from NaPi-IIa and NaPi-IIc. brush-border membrane; inorganic phosphate; sodium-dependent transport