Terrestrial life would be miserable without the ability to concentrate the urine. Glucocorticoids are the primary catabolic hormone that causes protein breakdown and ureagenesis. Urea excretion into the urine is the primary mechanism for eliminating this excess nitrogen from the body. A urea transporter is critically important to the theories proposed to explain the physiologic processes occurring when urine is concentrated. Only 14 years ago, evidence for such a transporter was largely speculative, but we provided experimental evidence that there is facilitated urea transport in the kidney inner medullary collecting duct. Subsequently, cDNA isoforms for facilitated urea transporters were cloned from kidney medulla (UT-A1, UT-A2, UT-A3, UT-A4), testis (UT-A5), and erythrocytes (UT-B). Recently, we cloned the rat and human genes for the UT-A family of urea transporters and showed that there are 2 promoters: promoter I, located 5' to exon 1, that controls transcription of UT-A1, UT-A3, and UT-A4; and promoter II, located in intron 12, that controls transcription of UT-A2. Our group has also made major progress in understanding the long-term regulation of urea transport by studying 5 animal models associated with an impaired urine concentrating ability. Our studies led to the surprising result that facilitated urea permeability and UT-A1 protein abundance are increased during in vivo conditions associated with a reduced urine concentrating ability and plasma vasopressin level. We also found that UT-A1 protein abundance is decreased during in vivo conditions associated with increased glucocorticoids.
| Mistry, Abinash C; Mallick, Rickta; Frohlich, Otto et al. (2007) The UT-A1 urea transporter interacts with snapin, a SNARE-associated protein. J Biol Chem 282:30097-106 |
| Klein, J D; Kozlowski, S; Antoun, T Abi et al. (2006) Adrenalectomy blocks the compensatory increases in UT-A1 and AQP2 in diabetic rat kidney. J Membr Biol 212:139-44 |
| Yang, James Y; Tam, W Y; Tam, Sidney et al. (2006) Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism. Am J Physiol Renal Physiol 291:F186-95 |
| Doran, John J; Klein, Janet D; Kim, Young Hee et al. (2006) Tissue distribution of UT-A and UT-B mRNA and protein in rat. Am J Physiol Regul Integr Comp Physiol 290:R1446-59 |
| Seshadri, Ramanathan M; Klein, Janet D; Smith, Tekla et al. (2006) Changes in subcellular distribution of the ammonia transporter, Rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol 290:F1443-52 |
| Seshadri, Ramanathan M; Klein, Janet D; Kozlowski, Shelley et al. (2006) Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. Am J Physiol Renal Physiol 290:F397-408 |
| Sands, Jeff M; Bichet, Daniel G; American College of Physicians et al. (2006) Nephrogenic diabetes insipidus. Ann Intern Med 144:186-94 |
| Chen, Guangping; Frohlich, Otto; Yang, Yuan et al. (2006) Loss of N-linked glycosylation reduces urea transporter UT-A1 response to vasopressin. J Biol Chem 281:27436-42 |
| Klein, Janet D; Murrell, Brian P; Tucker, Suzanne et al. (2006) Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension. Am J Physiol Renal Physiol 291:F952-9 |
| Klein, Janet D; Frohlich, Otto; Blount, Mitsi A et al. (2006) Vasopressin increases plasma membrane accumulation of urea transporter UT-A1 in rat inner medullary collecting ducts. J Am Soc Nephrol 17:2680-6 |
Showing the most recent 10 out of 25 publications
