| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Program in Membrane Biology and Renal Unit, Massachusetts General Hospital, Charlestown, MA, USA
3 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: paf10{at}pitt.edu.
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+ did not affect basal, i.e., PTH-independent JPi. Gd3+ had no effect on Jv when added to lumen or bath. Dopamine-inhibitable JPi was not affected by Gd3+. Experiments with proximal-like OK cells showed that elevated extracellular Ca2+ or NPS R467, a type II calcimimetic, inhibited PTH action on Pi uptake. In conclusion, PTH Type 1 receptors 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.
This article has been cited by other articles:
|
|
 |
|
  S. Smajilovic and J. Tfelt-Hansen Novel Role of the Calcium-Sensing Receptor in Blood Pressure Modulation Hypertension, December 1, 2008; 52(6): 994 - 1000. [Full Text] [PDF]
|
|
|
|
 |
|
 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 |
| Visit Other APS Journals Online |
