Urea and urine concentrating ability in mice lacking AQP1 and AQP3.
Aquaporin-1 (AQP1) and aquaporin-3 (AQP3) water channels expressed in the kidney play a critical role in the urine concentrating mechanism. Mice with AQP1 or AQP3 deletion have a urinary concentrating defect. To better characterize this defect, we studied the influence of an acute urea load (300 mumol ip) in conscious AQP1-null, AQP3-null, and wild-type mice. Urine was collected and assayed every 2 h, from 2 h before (baseline) to 8 h after the urea load. Mice of all genotypes excreted the urea load in approximately 4 h with the same time course. Interestingly, despite their low baseline, the AQP3-null mice raised their urine osmolality and urea concentration progressively after the urea load to values almost equal to those in wild-type mice at 8 h. In contrast, urine non-urea solute concentration did not change. Urine volume fell in the last 4 h to about one-fourth of basal values. AQP1-null mice increased their urine flow rate much more than AQP3-null mice and showed no change in urine osmolality and urea concentration. The urea load strongly upregulated urea transporter UT-A3 expression in all three genotypes. These observations show that the lack of AQP3 does not interfere with the ability of the kidney to concentrate urea but impairs its ability to concentrate other solutes. This solute-selective response could result from the capacity of AQP3 to transport not only water but also urea. The results suggest a novel role for AQP3 in non-urea solute concentration in the urine.
Zhao
Dan
D
Department of Medicine, University of California, San Francisco 94143-0521, USA.
Bankir
Lise
L
Qian
Liman
L
Yang
Dayu
D
Yang
Baoxue
B
D000818:Animals; D051398:Aquaporin 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051400:Aquaporin 3 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D001692:Biological Transport; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007668:Kidney / Q000737:chemistry / Q000503:physiopathology; D007671:Kidney Concentrating Ability / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017483:Receptors, Vasopressin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014508:Urea / Q000378:metabolism*; D014556:Urine / Q000737:chemistry*; D000096982:Urea Transporters
D051398:Aquaporin 1; D051400:Aquaporin 3; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014508:Urea; D000096982:Urea Transporters; C496021:Aqp1 protein, mouse; C496028:Aqp3 protein, mouse