Parathyroid hormone action on phosphate transporter mRNA and protein in rat renal proximal tubules

SA Kempson, M Lotscher, B Kaissling… - American Journal …, 1995 - journals.physiology.org
SA Kempson, M Lotscher, B Kaissling, J Biber, H Murer, M Levi
American Journal of Physiology-Renal Physiology, 1995journals.physiology.org
The inhibitory action of parathyroid hormone (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 whether this decrease represents decreased
activity of Na-Pi cotransporters already present in the BBM or whether 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 …
The inhibitory action of parathyroid hormone (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 whether this decrease represents decreased activity of Na-Pi cotransporters already present in the BBM or whether 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 1,315 +/- 44 in PTX rats, compared with 721 +/- 94 pmol.mg-1.10 s-1 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.(ABSTRACT TRUNCATED AT 250 WORDS)
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