Urea Transport and Clinical Potential of Urearetics #MMPMID27367911
Klein JD; Sands JM
Curr Opin Nephrol Hypertens 2016[Sep]; 25 (5): 444-51 PMID27367911show ga
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 UT-A and 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 post-translational modifications that increase its function by increasing UT-A1 accumulation in the apical plasma membrane. UT-A1 is phosphorylated by PKA, Epac, PKC?, and AMPK, 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 knock-out 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 agents.
free
free
free
Curr+Opin+Nephrol+Hypertens 2016 ; 25 (5): 444-51
