Hyperosmotic NaCl and urea synergistically regulate the expression of the UT-A2 urea transporter in vitro and in vivo.
The UT-A2 urea transporter is involved in the recycling of urea through the kidney, a process required to maintain high osmotic gradients. Dehydration increases UT-A2 expression in vivo. The tissue distribution of UT-A2 suggested that hyperosmolarity, and not vasopressin, might mediate this effect. We have analyzed the regulation of UT-A2 expression by ambiant osmolarity both in vitro (mIMCD3 cell line) and in vivo (rat kidney medulla). The UT-A2 mRNA was found to be synergistically up-regulated by a combination of NaCl and urea. Curiously, the UT-A2 protein was undetectable in this hypertonic culture condition, or after transfection of the UT-A2 cDNA, whereas it could be detected in HEK-293 transfected cells. Treating rats with furosemide, a diuretic which decreases the kidney interstitium osmolarity without affecting vasopressin levels, led to decreased levels of the UT-A2 protein. Our results show that the UT-A2 urea transporter is regulated by hyperosmolarity both in vitro and in vivo.
Leroy
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Service de Biologie Cellulaire, CEA/Saclay, Bâtiment 532, Gif sur Yvette Cedex, 91191, France.
Basset
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Gruel
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Ripoche
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Trinh-Trang-Tan
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Rousselet
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D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D009994:Osmolar Concentration; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D014508:Urea / Q000494:pharmacology*; D000096982:Urea Transporters
D002352:Carrier Proteins; D004232:Diuretics; D005665:Furosemide; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D012313:RNA; D012965:Sodium Chloride; D014508:Urea; D000096982:Urea Transporters