Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differences in dietary protein level induce differences in fractional excretion of urea, in arginine vasopressin (AVP) plasma level, and in urine concentrating activity (in which intervene the renal urea transporters (UT)). The abundance of mRNA for UT-A1 (of the inner medullary collecting duct, IMCD) UT-A2 (of the descending thin limb) and UT-B1 (of descending vasa recta) was determined by Northern analysis of total RNA extracted from medullary subregions of Sprague-Dawley rats fed for 1 week, a low, normal, or high protein diet. The implication of AVP was then examined by studying AVP-deprived (Brattleboro) rats. Our results show that none of these transporters is affected by the level of protein intake, except UT-A1 that is reduced in terminal IMCD by low protein diet in the absence of AVP (Brattleboro rats). These data suggest that (1) the previously reported effect of kidney medulla hypertonicity on UT-A2 and UT-B1 mRNA expression is somehow obliterated by protein intake deficiency or excess, and (2) AVP influences the mRNA abundance of the UT-A1 of the terminal IMCD during protein deficiency.
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PMID:mRNA expression of renal urea transporters in normal and Brattleboro rats: effect of dietary protein intake. 989 13

The rat renal urea transporter UT-A includes four isoforms. UT-A1, UT-A3, and UT-A4 are transcribed from a single initiation site at the 5'-end of the gene; a distinct internal initiation site is used for UT-A2 transcription. We cloned 1.3 kilobases (kb) of the 5'-flanking region upstream of the transcription start site of UT-A1, UT-A3, and UT-A4. This region contains three CCAAT sequences but lacks a TATA motif. A tonicity-responsive enhancer (TonE) was identified at -377bp. The 1.3-kb full fragment subcloned into pGL3 vector induced luciferase activity in Madin-Darby canine kidney cells and in mouse inner medullary collecting duct cells in isotonic medium. Luciferase activity was increased significantly in hypertonic medium, whereas deletion or mutation of the TonE sequence abolished this response. Electrophoretic mobility shift assay using the 5' UT-A TonE sequence as DNA probe showed formation of a specific DNA-protein complex with nuclear extracts from cells exposed to hypertonic medium and was weakly detectable in isotonic controls. A supershift in the mobility of the DNA-protein complex was observed with antiserum targeted to the TonE-binding protein (TonEBP). Co-transfection with dominant-negative TonEBP abolished the luciferase activity induced by the UT-A 1.3-kb construct under hypertonic and isotonic conditions. These data suggest that the TonE/TonEBP pathway mediates tonicity-responsive transcriptional regulation of UT-A1, UT-A3, and UT-A4 expression.
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PMID:The TonE/TonEBP pathway mediates tonicity-responsive regulation of UT-A urea transporter expression. 1099 47

Clinical disorders of extracellular fluid (ECF) volume regulation are often associated with changes in plasma urea concentration. To investigate possible renal causes, we measured the relative abundance of the urea transporters UT-A1, UT-A2, and UT-A3 in renal medulla of rats with aldosterone-induced NaCl retention. ECF volume-expanded rats received aldosterone by osmotic minipump plus a diet containing a high level of NaCl. Control rats received the same infusion of aldosterone plus a virtually NaCl-free diet, which prevented ECF volume expansion. Preliminary measurements demonstrated transient positive Na and water balance, decreased serum urea concentration, and increased urea clearance, but no change in creatinine clearance. Immunoblotting of homogenates from inner medulla showed a marked decrease in the abundance of the collecting duct urea transporters UT-A1 and UT-A3. There were no differences in the abundance of UT-A2, aquaporin (AQP)-2, AQP-3, or AQP-4 in ECF volume-expanded rats vs. controls. Time course experiments demonstrated that changes in UT-A1 abundance paralleled the fall in serum urea concentration after the switch from a low-NaCl to a high-NaCl diet, whereas the fall in UT-A3 abundance was delayed. Candesartan administration markedly decreased the abundance of UT-A1 and UT-A3 in the renal inner medulla, which is consistent with a role for the angiotensin II type 1 receptor in urea transport regulation. The results support the view that ECF-related changes in serum urea concentration are mediated, at least in part, through altered urea transporter abundance.
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PMID:Decreased abundance of collecting duct urea transporters UT-A1 and UT-A3 with ECF volume expansion. 1188 Mar 17

Dexamethasone treatment increases urea excretion and decreases urea permeability and urea transporter UT-A1 protein abundance in the inner medullary collecting duct (IMCD) of adrenalectomized rats. We examined the effect of dexamethasone treatment for 3 days on the abundance of several UT-A mRNA transcripts in rat renal medulla. By Northern blot analysis, a significant decrease in mRNA expression was observed in the inner medulla of dexamethasone-treated rats compared with controls for UT-A1 (71%), UT-A3 (75%), and UT-A3b (75%), but not for UT-A2. We then tested the effect of 100 nM dexamethasone on the activity of promoter I in the UT-A gene, using LLC-PK(1)-GR101 cells that express the glucocorticoid receptor. Dexamethasone significantly decreased the activity of rat UT-A promoter I (72%) but did not affect UT-A promoter II. Deletion analysis and site-directed mutagenesis demonstrated that sequences between -423 and -244 are important for this inhibition and that a 10-bp sequence at -363, which binds a nuclear protein in a gel shift assay, is necessary for basal promoter activity. The specific factors involved in repression of UT-A promoter I activity by glucocorticoids remain to be determined.
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PMID:Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene. 1193 95

Senescent female WAG/Rij rats exhibit polyuria without obvious renal disease or defects in vasopressin plasma level or V(2) receptor mRNA expression. Normalization of urine flow rate by 1-desamino-8-d-arginine vasopressin (dDAVP) was investigated in these animals. Long-term dDAVP infusion into 30-mo-old rats reduced urine flow rate and increased urine osmolality to levels comparable to those in control 10-mo-old rats. The maximal urine osmolality in aging rat kidney was, however, lower than that in adult kidney, despite supramaximal administration of dDAVP. This improvement involved increased inner medullary osmolality and urea sequestration. This may result from upregulation of UT-A1, the vasopressin-regulated urea transporter, in initial inner medullary collecting duct (IMCD), but not in terminal IMCD, where UT-A1 remained low. Expression of UT-A2, which contributes to medullary urea recycling, was greatly increased. Regulation of IMCD aquaporin (AQP)-2 (AQP2) expression by dDAVP differed between adult and senescent rats: the low AQP2 abundance in senescent rats was normalized by dDAVP infusion, which also improved targeting of the channel; in adult rats, AQP2 expression was unaltered, suggesting that IMCD AQP2 expression is not regulated by dDAVP directly. Increased AQP3 expression in senescent rats may also be involved in improved urine-concentrating capacity owing to higher basolateral water and urea reabsorption capacity.
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PMID:Correction of age-related polyuria by dDAVP: molecular analysis of aquaporins and urea transporters. 1238 83

Carrier-mediated urea transport allows rapid urea movement across the cell membrane, which is particularly important in the process of urinary concentration and for rapid urea equilibrium in non-renal tissues. Urea transporters mediate passive urea uptake that is inhibited by phloretin and urea analogues. Facilitated urea transporters are divided into two classes: (1) the renal tubular/testicular type of urea transporter, UT-A1 to -A5, encoded by alternative splicing of the SLC14A2 gene, and (2) the erythrocyte urea transporter UT-B1 encoded by the SLC14A1 gene. The primary structure of urea transporters is unique, consisting of two extended, hydrophobic, membrane-spanning domains and an extracellular glycosylated-connecting loop. UT-A1 is the result of a gene duplication of this two-halves-structure, and the duplicated portions are linked together by a large intracellular hydrophilic loop, carrying several putative protein kinase A (PKA) and -C (PKC) phosphorylation sites. UT-A1 is located in the apical membrane of the kidney inner medullary collecting duct cells, where it is stimulated acutely by cAMP-mediated phosphorylation in response to the antidiuretic hormone vasopressin. Vasopressin also up-regulates UT-A2 mRNA/protein expression in the descending thin limb of the loops of Henle. UT-A1 and UT-A2 are regulated independently and respond differently to changes in dietary protein content. UT-A3 and UT-A4 are located in the rat kidney medulla and UT-A5 in the mouse testis. The widely expressed UT-B participates in urea recycling in the descending vasa recta, as demonstrated by a relatively mild "urea-selective" urinary concentrating defect in transgenic UT-B null mice and individuals with the Jk(null) blood group.
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PMID:The SLC14 gene family of urea transporters. 1285 82

Urea transport in the kidney is mediated by a family of transporter proteins that include the renal urea transporter (UT-A) and the erythrocyte urea transporter (UT-B). The purpose of this study was to determine the location of the urea transporter isoforms in the mouse kidney and to examine the effects of prolonged potassium depletion on the expression and distribution of these transporters by ultrastructural immunocytochemistry. C57BL6 mice were fed a low-potassium diet for 2 wk, and control animals received normal chow. After 2 wk on a low-potassium diet, urinary volume increased and urinary osmolality decreased (833 +/- 30 vs. 1,919 +/- 174 mosmol/kgH2O), as previously demonstrated. Kidneys were processed for immunocytochemistry with antibodies against UT-A1 (L446), UT-A1 and UT-A2 (L194), UT-A3 (Q2), and UT-B. In normal mice, UT-A1 and UT-A3 were expressed mainly in the cytoplasm of the terminal inner medullary collecting duct (IMCD). UT-A2 immunoreactivity was observed mainly on the basolateral membrane of the type 1 epithelium of the descending thin limb (DTL) of short-looped nephrons. The intensity of UT-A1 and UT-A3 immunoreactivity in the IMCD was markedly reduced in potassium-depleted mice. In contrast, there was a significant increase in UT-A2 immunoreactivity in the DTL. The intensity of UT-B immunoreactivity in the descending vasa recta (DVR) was reduced in potassium-depleted animals compared with controls. In control animals, UT-B immunoreactivity was predominantly observed in the plasma membrane, whereas in potassium-depleted mice, it was mainly observed in cytoplasmic granules in endothelial cells of the DVR. In summary, potassium depletion is associated with reduced expression of UT-A1, UT-A3, and UT-B but increased expression of UT-A2. We conclude that reduced expression of urea transporters may play a role in the impaired urine-concentrating ability associated with potassium deprivation.
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PMID:Expression of urea transporters in potassium-depleted mouse kidney. 1295 54

The UT-B urea transporter is the major urea transporter in red blood cells and kidney descending vasa recta. Humans and mice that lack UT-B have a mild urine-concentrating defect. Whether deletion of UT-B altered the expression of other transporter proteins involved in urinary concentration was tested. Fluorescence-based real-time reverse transcription-PCR and Northern blot analysis showed upregulation of the UT-A2 urea transporter and the aquaporin 2 (AQP2) and AQP3 water channel transcripts but no change in other urea transporters or AQP. Western blot analysis showed that UT-A2 protein abundance in the outer medulla of UT-B null mice increased to 122 +/- 6% of wild-type control. AQP2 protein abundance increased to 177 +/- 32% and 127 +/- 7% in the outer and inner medulla, respectively, of UT-B null versus wild-type mice. The abundance of UT-A1, AQP1, renal outer medullary potassium channel, and NKCC2/BSC1 proteins were not significantly different between UT-B null and wild-type mice. The increases in AQP2 and AQP3 would reduce water loss and improve concentrating ability. The lack of UT-B does not result in a change in expression of urea transporters involved in urea reabsorption from the inner medullary collecting duct (UT-A1 and UT-A3). However, UT-B null mice have a selective increase in UT-A2 protein abundance. This may be an adaptive response to the loss of UT-B, because UT-B and UT-A2 are involved in different intrarenal urea recycling pathways.
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PMID:Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B. 1510 Mar 56

Urea transport in the kidney is mediated by a family of transporter proteins, including renal urea transporters (UT-A) and erythrocyte urea transporters (UT-B). We aimed to determine whether hydration status affects the subcellular distribution of urea transporters. Male Sprague-Dawley rats were divided into three groups: dehydrated rats (WD) given minimum water, hydrated rats (WL) given 3% sucrose in water for 3 days before death, and control rats given free access to water. We labeled kidney sections with antibodies against UT-A1 and UT-A2 (L194), UT-A3 (Q2), and UT-B using preembedding immunoperoxidase and immunogold methods. In control animals, UT-A1 and UT-A3 immunoreactivities were observed throughout the cytoplasm in inner medullary collecting duct (IMCD) cells, and weak labeling was observed on the basolateral plasma membrane. UT-A2 immunoreactivity in the descending thin limbs (DTL) was observed mainly on the apical and basolateral membranes of type I epithelium, and very faint labeling was observed in the long-loop DTL at the border between the outer and inner medulla. UT-A1 immunoreactivity intensity was markedly lower, and UT-A3 immunoreactivity was higher in IMCD of WD vs. controls. UT-A2 immunoreactivity intensities in the plasma membrane and cytoplasm of type I, II, and III epithelia of DTL were greater in WD vs. controls. In contrast, UT-A1 expression was greater and UT-A2 and UT-A3 expressions were lower in WL vs. controls. The subcellular distribution of UT-A in DTL or IMCD did not differ between control and experimental animals. UT-B was expressed in the plasma membrane of the descending vasa recta of both control and experimental animals. UT-B intensity was higher in WD and lower in WL vs. controls. These data indicate that changes in hydration status over 3 days affected urea transporter protein expression without changing its subcellular distribution.
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PMID:Ultrastructural localization of UT-A and UT-B in rat kidneys with different hydration status. 1617 86

Anuran amphibians accumulate a large amount of urea in their extracellular fluids to avoid a severe dehydration under dry and hyper-saline environments. To clarify the mechanisms of urea retention, we examined structure and distribution of the urea transporter (UT) in the kidney of the marine toad (Bufo marinus), and its expression in the kidney and urinary bladder following exposure to dry and hyper-saline conditions by means of cDNA cloning, semi-quantitative RT-PCR, immunoblot analysis and immunohistochemistry. The Bufo UT cDNA cloned from the kidney encodes a 390-amino-acid residue protein, which is 80% identical to Rana esculenta UT with the functional characteristics of a urea transporter. The Bufo UT mRNA was abundantly expressed in the kidney and urinary bladder, but not in the skin. In immunoblot analysis using a specific antibody raised against the Bufo UT, a 52 kDa protein similar to the glycosylated forms of mammalian UT-A2 ( approximately 55 kDa) was detected in extracts from plasma membrane fractions of the kidney and urinary bladder. When toads were acclimated to dry and hyper-saline environments for 7 days, UT mRNA expression was upregulated in the kidney and urinary bladder and there was an elevated plasma urea concentration and osmolality. Immunohistochemistry showed that the UT was specifically localized on the apical membrane of the early distal tubule, known to be the diluting segment, in the kidney and the epithelial cells of urinary bladder. Immunoreactive cells were not detected along the late distal tubule, the connecting tubule or the collecting duct in the kidney. The present findings suggest that the Bufo UT probably contributes to urea transport in the kidney and urinary bladder in response to hyperosmotic stresses such as body fluid hypertonicity and dehydration.
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PMID:Effect of osmotic stress on expression of a putative facilitative urea transporter in the kidney and urinary bladder of the marine toad, Bufo marinus. 1654 93


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