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Am J Physiol Renal Physiol 292: F395-F403, 2007. First published September 19, 2006; doi:10.1152/ajprenal.00100.2006
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Parathyroid hormone-dependent endocytosis of renal type IIc Na-P_i cotransporter

¹Department of Molecular Nutrition, Institution of Health Biosciences, and ²Department of Clinical Nutrition, Institution of Health Biosciences, The University of Tokushima Graduate School, Tokushima City, Japan

Submitted 28 March 2006 ; accepted in final form 13 September 2006

Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-P_i cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-P_i cotransporter by parathyroid hormone (PTH). Type IIc Na-P_i cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1–34) (PKA and PKC activator) or PTH(3–34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-P_i cotransporter in renal proximal tubules.

phosphate transporter; proximal tubule; regulation

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