title: Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism.
abstract: 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.affiliation: Dept. of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Lu, Haidian District, Beijing, China.
authors.forename: Tianluo
authors.initials: T
authors.lastname: Lei
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Anita T
authors.initials: AT
authors.lastname: Layton
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Xuejian
authors.initials: X
authors.lastname: Zhao
authors.forename: Lise
authors.initials: L
authors.lastname: Bankir
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D005260:Female; D007671:Kidney Concentrating Ability; D008138:Loop of Henle / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014508:Urea / Q000378:metabolism; D000096982:Urea Transporters
chemical_list: D026901:Membrane Transport Proteins; D014508:Urea; D000096982:Urea Transporters; C452857:urea transporter B, mouse