Structure, regulation and physiological roles of urea transporters

Matthias A. Hediger, Craig P. Smith, Guofeng You, Wen Sen Lee, Yoshikatsu Kanai, Chairat Shayakul

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Urea is the major constituent of the urine and the principal means for disposal of nitrogen derived from amino acid metabolism. Specialized phloretin-inhibitable urea transporters are expressed in kidney medulla and play a central role in urea excretion and water balance. These transporters allow accumulation of urea in the medulla and enable the kidney to concentrate urine to an osmolality greater than systemic plasma. Recently, expression cloning with Xenopus oocytes has led to the isolation of a novel phloretin-inhibitable urea transporter (UT2) from rabbit, and subsequently from rat kidney. UT2 from both species has the characteristics of the phloretin-sensitive urea transporter previously defined in kidney by in vitro perfused tubule studies. Based on these advances, Ripoche and colleagues cloned a homologous urea transporter (HUT11) from erythrocytes. UT2 and HUT11 predict 43 kDa polypeptides and exhibit 64% amino acid sequence identity. Since regulation of urea transport in the kidney plays an important role in the orchestration of the antidiuretic response, we have studied the regulation of urea transporter in rat kidney at the mRNA level. On Northern blots probed at high stringency, rat UT2 hybridized to two transcripts of 2.9 kb and 4.0 kb, which have spatially distinct distributions within the kidney. Northern analysis and in situ hybridization of kidneys from rats maintained at different physiologic states revealed that the 2.9 and 4.0 kb transcripts are regulated by separate mechanisms. The 4 kb transcript was primarily responsive to changes in the dietary protein content, whereas the 2.9 kb transcript was highly responsive to changes in the hydration state of the animal. We propose that the two UT2 transcripts are regulated by distinct mechanisms to allow optimal fluid balance and urea excretion.

Original languageEnglish
Pages (from-to)1615-1623
Number of pages9
JournalKidney International
Volume49
Issue number6
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Urea
Phloretin
Kidney
Kidney Medulla
Urine
Water-Electrolyte Balance
Dietary Proteins
Xenopus
Northern Blotting
Osmolar Concentration
Oocytes
In Situ Hybridization
urea transporter
Organism Cloning
Amino Acid Sequence
Nitrogen
Erythrocytes
Rabbits
Amino Acids
Messenger RNA

ASJC Scopus subject areas

  • Nephrology

Cite this

Hediger, M. A., Smith, C. P., You, G., Lee, W. S., Kanai, Y., & Shayakul, C. (1996). Structure, regulation and physiological roles of urea transporters. Kidney International, 49(6), 1615-1623.

Structure, regulation and physiological roles of urea transporters. / Hediger, Matthias A.; Smith, Craig P.; You, Guofeng; Lee, Wen Sen; Kanai, Yoshikatsu; Shayakul, Chairat.

In: Kidney International, Vol. 49, No. 6, 1996, p. 1615-1623.

Research output: Contribution to journalArticle

Hediger, MA, Smith, CP, You, G, Lee, WS, Kanai, Y & Shayakul, C 1996, 'Structure, regulation and physiological roles of urea transporters', Kidney International, vol. 49, no. 6, pp. 1615-1623.
Hediger MA, Smith CP, You G, Lee WS, Kanai Y, Shayakul C. Structure, regulation and physiological roles of urea transporters. Kidney International. 1996;49(6):1615-1623.
Hediger, Matthias A. ; Smith, Craig P. ; You, Guofeng ; Lee, Wen Sen ; Kanai, Yoshikatsu ; Shayakul, Chairat. / Structure, regulation and physiological roles of urea transporters. In: Kidney International. 1996 ; Vol. 49, No. 6. pp. 1615-1623.
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