title: Urea may regulate urea transporter protein abundance during osmotic diuresis.
abstract: Rats with diabetes mellitus have an increase in UT-A1 urea transporter protein abundance and absolute urea excretion, but the relative amount (percentage) of urea in total urinary solute is actually decreased due to the marked glucosuria. Urea-specific signaling pathways have been identified in mIMCD3 cells and renal medulla, suggesting the possibility that changes in the percentage or concentration of urea could be a factor that regulates UT-A1 abundance. In this study, we tested the hypothesis that an increase in a urinary solute other than urea would increase UT-A1 abundance, similar to diabetes mellitus, whereas an increase in urine urea would not. In both inner medullary base and tip, UT-A1 protein abundance increased during NaCl- or glucose-induced osmotic diuresis but not during urea-induced osmotic diuresis. Next, rats undergoing NaCl or glucose diuresis were given supplemental urea to increase the percentage of urine urea to control values. UT-A1 abundance did not increase in these urea-supplemented rats compared with control rats. Additionally, both UT-A2 and UT-B protein abundances in the outer medulla increased during urea-induced osmotic diuresis but not in NaCl or glucose diuresis. We conclude that during osmotic diuresis, UT-A1 abundance increases when the percentage of urea in total urinary solute is low and UT-A2 and UT-B abundances increase when the urea concentration in the medullary interstitium is high. These findings suggest that a reduction in urine or interstitial urea results in an increase in UT-A1 protein abundance in an attempt to restore inner medullary interstitial urea and preserve urine-concentrating ability.
authors.affiliation: Emory University School of Medicine, Department of Medicine, Renal Division, 1639 Pierce Dr., NE, WMB Rm. 338, Atlanta, GA 30322, USA.
authors.forename: Dongun
authors.initials: D
authors.lastname: Kim
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Sandy
authors.initials: S
authors.lastname: Racine
authors.forename: Brian P
authors.initials: BP
authors.lastname: Murrell
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000652:urine; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D014508:Urea / Q000652:urine*; D000096982:Urea Transporters
chemical_list: D005947:Glucose; D026901:Membrane Transport Proteins; D012965:Sodium Chloride; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D014508:Urea; D000096982:Urea Transporters; C578716:Slc12a1 protein, rat