Role and Regulation of Urea Transporters

In the past few years, significant knowledge has been gained about the physiological role and regulation of urea transporters, which have been now cloned in many species. The two major mammalian urea transporters, UT-A and UT-B, have been best studied in the kidney, where they mediate the facilitated diffusion of urea across tubular, interstitial, and vascular compartments, necessary to maintain an osmolar gradient along the renal corticomedullary axis. The genes encoding these transporters, Slc14A2 for UT-A and Slc14A1 for UT-B, have been characterized in rodents and humans, allowing identification of transcriptional mechanisms involved in the regulation of UT-A expression. The crucial role that urea transporters play in renal physiology is underscored by the phenotypic characteristics of UT-A and UT-B knockout mice, in which lack of specific urea transporters impairs the ability to concentrate urine. Expression of the UT-A and UT-B transporters has also been identified in extra-renal sites, where their physiological significance is only beginning to be elucidated. More information on the mechanisms modulating urea transporter expression is becoming available, and the possible involvement of aberrant regulation of these transporters in pathological conditions, or as a result of certain pharmacological treatments, has emerged from recent studies.