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 (Pi) intake and parathyroid hormone (PTH) are essential regulators of proximal tubular (PT) Pi reabsorption; both factors are associated with adaptive changes in PT apical brush border membrane (BBM) Na/Pi-cotransport activity and specific transporter protein (NaPi-2) content. Urinary Pi 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-Pi (1.2%) versus low-Pi (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 Pi intake. These results suggest that reduced renal PT CaR expression by a high-Pi diet and by increased circulating PTH levels could contribute to the local control of PT handling of Ca2+ and Pi.
Riccardi
D
D
School of Biological Sciences, Manchester, UK. RICCARDI@fs1.scg.man.ac.uk
Traebert
M
M
Ward
D T
DT
Kaissling
B
B
Biber
J
J
Hebert
S C
SC
Murer
H
H
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis*; D004032:Diet; D005455:Fluorescent Antibody Technique; D007687:Kidney Tubules, Proximal / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D010281:Parathyroid Hormone / Q000097:blood / Q000494:pharmacology*; D028044:Phosphate-Binding Proteins; D010710:Phosphates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000032:analysis*; D012964:Sodium / Q000494:pharmacology*
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat; D012964:Sodium