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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

¹Laboratory of Molecular Toxicology, University of Zaragoza, Spain; ²Institute of Physiology and Center for Integrative Human Physiology, University of Zurich, Switzerland; and ³Department of Medicine, University of Colorado Health Sciences Center, Aurora, Colorado

Submitted 19 October 2008 ; accepted in final form 8 December 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 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_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.

brush-border membrane; inorganic phosphate; sodium-dependent transport

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