Renal urea transporters.
OBJECTIVE
Urea is transported across the kidney inner medullary collecting duct by urea-transporter proteins. Two urea-transporter genes have been cloned from humans and rodents: the UT-A (Slc14A2) gene encodes five protein and eight cDNA isoforms; the UT-B (Slc14A1) gene encodes a single isoform. In the past year, significant progress has been made in understanding the regulation of urea-transporter protein abundance in kidney, studies of genetically engineered mice that lack a urea transporter, identification of urea transporters outside of the kidney, cloning of urea transporters in nonmammalian species, and active urea transport in microorganisms.


RESULTS
UT-A1 protein abundance is increased by 12 days of vasopressin, but not by 5 days. Analysis of the UT-A1 promoter suggests that vasopressin increases UT-A1 indirectly following a direct effect to increase the transcription of other genes, such as the Na(+)-K(+)-2Cl- cotransporter NKCC2/BSC1 and the aquaporin (AQP) 2 water channel, that begin to increase inner medullary osmolality. UT-A1 protein abundance is also increased by adrenalectomy, and is decreased by glucocorticoids or mineralocorticoids. However, each hormone works through its own receptor. Knockout mice that lack UT-A1 and UT-A3, or lack UT-B, have a urine-concentrating defect and a decrease in inner medullary interstitial urea content.


CONCLUSIONS
Urea transporters play a critical role in the urine-concentrating mechanism. Their abundance is regulated by vasopressin, glucocorticoids, and mineralocorticoids. These regulatory mechanisms may be important in disease states such as diabetes because changes in urea-transporter abundance in diabetic rats require glucocorticoids and vasopressin.
Sands
Jeff M
JM
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. jeff.sands@emory.edu
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism; D000096982:Urea Transporters
D026901:Membrane Transport Proteins; D014667:Vasopressins; D000096982:Urea Transporters