Urea: new questions about an ancient solute

Urea recycling and counter-current exchange within the renal tubular, vascu lar and interstitial compartments help maintain high levels of this solute in the renal medulla, that are crucial for the production of concentrated u rine. The role of urea in physiological and pathological conditions is stil l unclear, although new information is becoming available, Several urea tra nsporters have been identified that mediate facilitated transport of urea a cross biological membranes in the mammalian kidney in amphibians, and in el asmobranchs, Evidence that urea transporters may be expressed iu other mamm alian organs is also beginning to emerge. The mechanisms involved in the re gulation of urea transport are incompletely understood, In this respect, th e structural and functional characterization of individual transporters is providing the basis to identify specific regulatory factors. Urea can be vi ewed as a perturbing osmolyte in the renal inner medulla, and the mechanism s of adaptation of renal cells to high concentration of this destabilizing solute are being investigated. Urea-specific signaling pathways have been i dentified, that could contribute to clarify how cells handle urea.