TY - JOUR
T1 - Structure, regulation and physiological roles of urea transporters
AU - Hediger, Matthias A.
AU - Smith, Craig P.
AU - You, Guofeng
AU - Lee, Wen Sen
AU - Kanai, Yoshikatsu
AU - Shayakul, Chairat
N1 - Funding Information:
It is a pleasure to acknowledge Drs. Mark Knepper, Jeff Sands, Pierre Ripoche and Jean-Pierre Cartron for their contribution to this work. We also thank Dr. Lise Bankir for stimulating discussion. This work was supported by the National Institutes of Diabetes and Digestive and Kidney Disease Grants DK43632, 43171 and 46289 to M.A. Hediger.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1038/ki.1996.235
DO - 10.1038/ki.1996.235
M3 - Article
C2 - 8743465
AN - SCOPUS:0029973442
SN - 0085-2538
VL - 49
SP - 1615
EP - 1623
JO - Kidney International
JF - Kidney International
IS - 6
ER -