title: Urea transport and clinical potential of urearetics.
abstract: 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.
  
  
  
  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.
  
  
  
  Urea transporters play critical roles in the urine-concentrating mechanism. Urea transport inhibitors are a promising new class of diuretic agent.
authors.affiliation: Renal Division, Department of Medicine, and Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004231:Diuresis; D004232:Diuretics / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D014508:Urea / Q000378:metabolism*; D000096982:Urea Transporters
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D004232:Diuretics; D026901:Membrane Transport Proteins; D011493:Protein Kinase C; D014508:Urea; D000096982:Urea Transporters