Parathyroid hormone action on phosphate transporter mrna and protein in rat
renal proximal tubules.
Kempson, Stephen A., Marius Lotscher, Brigitte Kaissling, Jurg Biber, Heini
Murer, and Moshe Levi.
Department of Physiology & Biophysics, Indiana University Medical Center,
Indianapolis, IN 46223; Institute of Physiology and Anatomy, University of
Zurich, CH-8057, Zurich, Switzerland; Department of Internal Medicine,
University of Texas Southwestern, Medical Center and VA Medical Center,
Dallas, TX 75216.
APStracts 2:0002F, 1995.
The inhibitory action of PTH on Pi reabsorption in the renal proximal tubule
is accompanied by a specific decrease in Na/Pi cotransport at the apical
brush border membrane (BBM). It is not known if this decrease represents
decreased activity of Na/Pi cotransporters already present in the BBM or if
the number of cotransporters is decreased. The present study of the molecular
mechanism of PTH action made use of a specific cDNA probe and antiserum to a
rat renal Na/Pi cotransporter (NaPi-2). Three groups of rats were used;
intact controls, chronically parathyroidectomized (PTX), and PTX rats treated
acutely (2 h) with bovine PTH (1-34). Na/Pi cotransport by isolated renal BBM
vesicles was increased to 1315+44 in PTX rats compared to 721+94 pmol/mg/10s
in controls (p<0.002), and was returned to control levels by PTH. Western
blots of these BBM showed that PTX caused a 2.8 - fold increase in NaPi-2
protein content which was reduced to control levels by PTH.
Immunohistochemistry of perfusion fixed kidneys showed NaPi-2 specific
immunofluorescence exclusively in apical BBM of proximal tubules. Expression
of NaPi-2 protein at these sites was increased in PTX rats and decreased
after PTH treatment. Northern analysis of total RNA showed that the abundance
of NaPi-2 specific mRNA was not changed by PTX but there was a small decrease
in response to PTH. The data indicate that PTH regulation of renal Na/Pi
cotransport is determined by changes in expression of NaPi-2 protein in the
renal BBM. PTH may decrease the NaPi-2 protein content of BBM in part by a
mechanism that results in endocytic withdrawal into a cytoplasmic pool.
Received 22 November 1994; accepted in final form 17 January 1995.
APS Manuscript Number F417-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.