Nanomolar Potency and Metabolically Stable Inhibitors of Kidney Urea Transporter UT-B
نویسندگان
چکیده
منابع مشابه
Triazolothienopyrimidine inhibitors of urea transporter UT-B reduce urine concentration.
Urea transport (UT) proteins facilitate the concentration of urine by the kidney, suggesting that inhibition of these proteins could have therapeutic use as a diuretic strategy. We screened 100,000 compounds for UT-B inhibition using an optical assay based on the hypotonic lysis of acetamide-loaded mouse erythrocytes. We identified a class of triazolothienopyrimidine UT-B inhibitors; the most p...
متن کاملUpregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B.
The UT-B urea transporter is the major urea transporter in red blood cells and kidney descending vasa recta. Humans and mice that lack UT-B have a mild urine-concentrating defect. Whether deletion of UT-B altered the expression of other transporter proteins involved in urinary concentration was tested. Fluorescence-based real-time reverse transcription-PCR and Northern blot analysis showed upre...
متن کاملRegulated expression of renal and intestinal UT-B urea transporter in response to varying urea load.
Production, recycling, and elimination of urea are important to maintain nitrogen balance. Adaptation to varying loads of urea due to different protein intake or in renal failure may involve changes in urea transport and may possibly affect urea transporters. In this study, we examined the expression of the UT-B urea transporter in rats fed a low-protein diet (LPD), a high-protein diet (HPD), a...
متن کاملExpression and localization of a UT-B urea transporter in the human bladder.
Facilitative UT-B urea transporters have been shown to play an important role in the urinary concentrating mechanism. Recent studies have now suggested a link between UT-B allelic variation and human bladder cancer risk. UT-B1 protein has been previously identified in the bladder of various mammalian species, but not yet in humans. The aim of the present study was to investigate whether any UT-...
متن کاملLocalization of the urea transporter UT-B protein in human and rat erythrocytes and tissues.
A new polyclonal antibody to the human erythrocyte urea transporter UT-B detects a broad band between 45 and 65 kDa in human erythrocytes and between 37 and 51 kDa in rat erythrocytes. In human erythrocytes, the UT-B protein is the Kidd (Jk) antigen, and Jk(a+b+) erythrocytes express the 45- to 65-kDa band. However, in Jk null erythrocytes [Jk(a-b-)], only a faint band at 55 kDa is detected. In...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2012
ISSN: 0022-2623,1520-4804
DOI: 10.1021/jm300491y