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.