Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na⁺-dependent P_i transporter (NaPi-2) in the rat proximal tubule

Abstract.

Dietary phosphate (P_i) intake and parathyroid hormone (PTH) are essential regulators of proximal tubular (PT) P_i reabsorption; both factors are associated with adaptive changes in PT apical brush border membrane (BBM) Na/P_i-cotransport activity and specific transporter protein (NaPi-2) content. Urinary P_i excretion is also inversely correlated with luminal Ca²⁺ concentration ([Ca²⁺]) both in a PTH-dependent and -independent fashion. A cell-surface, Ca²⁺(/polyvalent cation)-sensing receptor (CaR) has been localized to the PT BBM with unknown function. To investigate whether PTH and/or dietary Pi intake could affect the distribution or the expression of the CaR, we evaluated their effects on rat kidney CaR and the NaPi-2 expression by Western blot analysis and immunofluorescence microscopy. A chronic high-P_i (1.2%) versus low-P_i (0.1%) diet and acute PTH (1–34) infusion significantly reduced the PT BBM expression of both NaPi-2 and CaR proteins. CaR-specific immunoreactivity in nephron segments other than the PT was not affected by PTH or P_i intake. These results suggest that reduced renal PT CaR expression by a high-P_i diet and by increased circulating PTH levels could contribute to the local control of PT handling of Ca²⁺ and P_i.