| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1Pharmacology and 3Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; and 2Program in Membrane Biology and Renal Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129
Submitted 15 July 2003 ; accepted in final form 1 September 2003
Inorganic phosphate (Pi) is absorbed by proximal tubules through a cellular pathway that is inhibited by parathyroid hormone (PTH). The calcium-sensing receptor (CaSR) is expressed on apical membranes of proximal tubules. In the present studies, we determined the effect of luminal and/or basolateral PTH on phosphate absorption and tested the hypothesis that CaSR activation blocks PTH-inhibitable phosphate absorption. Single proximal S3 tubules were dissected from the kidneys of mice and studied by the Burg technique. Tubules were bathed with DMEM culture media supplemented with 6% BSA and perfused with an ultrafiltrate prepared from the bathing solution. 33P and FITC-inulin were added to the luminal perfusate to measure phosphate absorption (JPi) and fluid absorption (Jv), respectively. JPi averaged 2.9 pmol·min–1·mm–1 under control conditions and decreased by 20% upon addition of serosal PTH. PTH had no effect on Jv. Inclusion of PTH in the luminal perfusate reduced JPi to 2.1 pmol · min–1 · mm–1. Combined addition of PTH to perfusate and bathing solutions reduced JPi to 1.5 pmol · min–1 · mm–1 without affecting Jv. Indirect immunofluorescence studies revealed abundant PTH receptor (PTH1R) expression on brush-border membranes, with lower amounts on basolateral membranes. CaSRs were localized primarily, but not exclusively, to brush-border membranes. CaSR activation with luminal Gd3+ abolished the inhibitory action of PTH on JPi. Addition of Gd3+ to the serosal bathing solution had no effect on PTH-sensitive JPi. Gd3+ i.e., PTH-independent JPi. Gd3+ did not affect basal, had no effect on Jv when added to lumen or bath. Dopamine-inhibitable JPi was not affected by Gd3+. Experiments with proximal-like opossum kidney cells showed that elevated extracellular Ca2+ or NPS R467, a type II calcimimetic, inhibited PTH action on Pi uptake. In conclusion, PTH1Rs are expressed on apical and basolateral membranes of mouse proximal tubules. Stimulating apical or basolateral PTH1R inhibits phosphate absorption. CaSR activation specifically regulates PTH-suppressible phosphate absorption.
kidney; parathyroid hormone; opossum kidney cells; dopamine; parathyroid hormone receptor
This article has been cited by other articles:
|
|
 |
|
  M. J. Mahon Ezrin promotes functional expression and parathyroid hormone-mediated regulation of the sodium-phosphate cotransporter 2a in LLC-PK1 cells Am J Physiol Renal Physiol, March 1, 2008; 294(3): F667 - F675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Smajilovic and J. Tfelt-Hansen Calcium acts as a first messenger through the calcium-sensing receptor in the cardiovascular system Cardiovasc Res, August 1, 2007; 75(3): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. J. Hoenderop, B. Nilius, and R. J. M. Bindels Calcium Absorption Across Epithelia Physiol Rev, January 1, 2005; 85(1): 373 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Biber, S. M. Gisler, N. Hernando, C. A. Wagner, and H. Murer PDZ interactions and proximal tubular phosphate reabsorption Am J Physiol Renal Physiol, November 1, 2004; 287(5): F871 - F875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Chen and W. G. Goodman Role of the calcium-sensing receptor in parathyroid gland physiology Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1005 - F1011. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
