Document Detail


Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism.
MedLine Citation:
PMID:  21849488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts.
Authors:
Tianluo Lei; Lei Zhou; Anita T Layton; Hong Zhou; Xuejian Zhao; Lise Bankir; Baoxue Yang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-17
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  301     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-02-01     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1251-9     Citation Subset:  IM    
Affiliation:
Dept. of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Lu, Haidian District, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Kidney Concentrating Ability*
Loop of Henle / metabolism*
Membrane Transport Proteins / genetics,  metabolism*
Mice
Mice, Knockout
Urea / metabolism
Grant Support
ID/Acronym/Agency:
DK089066/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Transport Proteins; 0/urea transporter; 0/urea transporter B, mouse; 57-13-6/Urea
Comments/Corrections

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