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Urea Transport and Clinical Potential of Urearetics

Janet D Klein, Jeff M Sands

Curr Opin Nephrol Hypertens. 2016 Sep;25(5):444-51.

PMID: 27367911

Abstract:

Purpose of review:
Urea is transported by urea transporter proteins in kidney, erythrocytes, and other tissues. Mice in which different urea transporters have been knocked out have urine-concentrating defects, which has led to the development and testing of urea transporters Slc14A2 (UT-A) and Slc14A1 (UT-B) inhibitors as urearetics. This review summarizes the knowledge gained during the past year on urea transporter regulation and investigations into the clinical potential of urearetics.
Recent findings:
UT-A1 undergoes several posttranslational modifications that increase its function by increasing UT-A1 accumulation in the apical plasma membrane. UT-A1 is phosphorylated by protein kinase A, exchange protein activated by cyclic AMP, protein kinase Cα, and AMP-activated protein kinase, all at different serine residues. UT-A1 is also regulated by 14-3-3, which contributes to UT-A1 removal from the membrane. UT-A1 is glycosylated with various glycan moieties in animal models of diabetes mellitus. Transgenic expression of UT-A1 into UT-A1/UT-A3 knockout mice restores urine-concentrating ability. UT-B is present in descending vasa recta and urinary bladder, and is linked to bladder cancer. Inhibitors of UT-A and UT-B have been developed that result in diuresis with fewer abnormalities in serum electrolytes than conventional diuretics.
Summary:
Urea transporters play critical roles in the urine-concentrating mechanism. Urea transport inhibitors are a promising new class of diuretic agent.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP145164245 A3 Glycan A3 Glycan 145164-24-5 Price
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