title: Parathyroid hormone action on phosphate transporter mRNA and protein in rat renal proximal tubules.
abstract: 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)
authors.affiliation: Department of Physiology and Biophysics, Indiana University Medical Center, Indianapolis 46223, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Kempson
authors.forename: M
authors.initials: M
authors.lastname: Lötscher
authors.forename: B
authors.initials: B
authors.lastname: Kaissling
authors.forename: J
authors.initials: J
authors.lastname: Biber
authors.forename: H
authors.initials: H
authors.lastname: Murer
authors.forename: M
authors.initials: M
authors.lastname: Levi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007672:Kidney Cortex; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016105:Parathyroidectomy; D028044:Phosphate-Binding Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D010281:Parathyroid Hormone; D028044:Phosphate-Binding Proteins; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters