Cloning and regulation of expression of the rat kidney urea transporter (rUT2)

C. P. Smith, W. S. Lee, S. Martial, M. A. Knepper, G. You, J. M. Sands, M. A. Hediger

Research output: Contribution to journalArticle

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Abstract

In mammals, urea is the predominant end-product of nitrogen metabolism and plays a central role in the urinary-concentrating mechanism. Urea accumulation in the renal medulla is critical to the ability of the kidney to concentrate urine to an osmolality greater than systemic plasma. Regulation of urea excretion and accumulation in the renal medulla depends on the functional state of specialized phloretin-sensitive urea transporters. To study these transporters and their regulation of expression we isolated a cDNA which encodes the rat homologue (rUT2) of rabbit UT2 (You, G., C. P. Smith, Y. Kanai, W.-S. Lee, M. Stelzner, and M. A. Hediger, et al. Nature (Lond.). 1993, 365:844-847). Rat UT2 has 88% amino acid sequence identity to rabbit UT2 and 64% identity to the recently cloned human erythrocyte urea transporter, HUT11 (Olives, B., P. Neav, P. Bailly, M. A. Hediger, G. Rousselet, J. P. Cartron, and P. Ripoch J. Biol. Chem. 1994. 269:31649- 31652). Analysis of rat kidney mRNA revealed two transcripts of size 2.9 and 4.0 kb which had spatially distinct distributions. Northern analysis and in situ hybridization showed that the 4.0-kb transcript was primarily responsive to changes in the protein content of the diet whereas the 2.9-kb transcript was responsive to changes in the hydration state of the animal. These studies reveal thai the expression levels of the two rUT2 transcripts are modulated by different pathways to allow fluid and nitrogen balance to be regulated independently. Our data provide important insights into the regulation of the renal urea transporter UT2 and provide a basis on which to refine our understanding of the urinary concentrating mechanism and its regulation.

Original languageEnglish
Pages (from-to)1556-1563
Number of pages8
JournalJournal of Clinical Investigation
Volume96
Issue number3
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Organism Cloning
Kidney
Urea
Nitrogen
Phloretin
Rabbits
Water-Electrolyte Balance
Olea
Osmolar Concentration
In Situ Hybridization
Mammals
Amino Acid Sequence
Complementary DNA
Erythrocytes
urea transporter
Urine
Diet
Messenger RNA
Proteins

Keywords

  • colon
  • membrane transport protein
  • nitrogen metabolism
  • urea
  • urinary concentrating mechanism

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Smith, C. P., Lee, W. S., Martial, S., Knepper, M. A., You, G., Sands, J. M., & Hediger, M. A. (1995). Cloning and regulation of expression of the rat kidney urea transporter (rUT2). Journal of Clinical Investigation, 96(3), 1556-1563.

Cloning and regulation of expression of the rat kidney urea transporter (rUT2). / Smith, C. P.; Lee, W. S.; Martial, S.; Knepper, M. A.; You, G.; Sands, J. M.; Hediger, M. A.

In: Journal of Clinical Investigation, Vol. 96, No. 3, 1995, p. 1556-1563.

Research output: Contribution to journalArticle

Smith, CP, Lee, WS, Martial, S, Knepper, MA, You, G, Sands, JM & Hediger, MA 1995, 'Cloning and regulation of expression of the rat kidney urea transporter (rUT2)', Journal of Clinical Investigation, vol. 96, no. 3, pp. 1556-1563.
Smith CP, Lee WS, Martial S, Knepper MA, You G, Sands JM et al. Cloning and regulation of expression of the rat kidney urea transporter (rUT2). Journal of Clinical Investigation. 1995;96(3):1556-1563.
Smith, C. P. ; Lee, W. S. ; Martial, S. ; Knepper, M. A. ; You, G. ; Sands, J. M. ; Hediger, M. A. / Cloning and regulation of expression of the rat kidney urea transporter (rUT2). In: Journal of Clinical Investigation. 1995 ; Vol. 96, No. 3. pp. 1556-1563.
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