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

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 P-i 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.