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

We investigated the diversity of cellular localization of the GLUT-1 glucose transporter protein at epithelial and endothelial barriers either possessing or lacking occluding junctions. The avidin-biotin immunoperoxidase and the immunogold-silver staining (IGSS) techniques were used. A rabbit polyclonal antiserum prepared against a synthetic peptide encoding the 13 amino acids at the carboxyl terminus of the GLUT-1 glucose transporter protein was used. Both techniques were found to have comparable sensitivity in detecting immunoreactive GLUT-1. The IGSS experiments employed a light-insensitive stabilizer, and no immunoreactive GLUT-1 was found in brain cells (neurons, glial cells), but abundant immunoreactive GLUT-1 was found in brain capillary endothelium, which is composed of cells with occluding junctions. However, immunoreactive GLUT-1 was also found in endothelium known not to contain occluding junctions, such as testicular microvascular endothelium and endothelium on the fetal side of the syncytiotrophoblast of the placenta. In epithelial barriers, GLUT-1 was also found in the basolateral membrane of renal collecting duct epithelium, choroid plexus, and the placental syncytiotrophoblast layer. However, immunoreactive GLUT-1 was found in the apical membrane of ependymal epithelium near the lower portion of the third ventricle. In conclusion, there is diversity underlying the expression of the GLUT-1 glucose transporter protein in different cell types, and the transporter protein can be found in endothelium with and without occluding junctions, and in both apical and basolateral membranes of epithelial barriers.
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PMID:GLUT-1 glucose transporter is present within apical and basolateral membranes of brain epithelial interfaces and in microvascular endothelia with and without tight junctions. 155 63

Acidification of the urine is mediated by vectorial H+ transport from cells at a number of sites in the kidney. A proton ATPase has been described that appears to mediate a significant proportion of this H+ transport. In particular, in proximal tubule and collecting duct, there is evidence both for the presence of transporter protein and for H+ transport with features that have been identified with it. This review highlights some of the unresolved questions regarding this transporter, specifically, its distribution and relationship to the vacuolar pump present in endocytotic vesicles, how physiologic control is asserted, and its role in pathophysiology. The review discusses in greater detail the issue of whether the vacuolar H+ ATPase is responsible for all of the urinary acidification and concludes that it probably is not. Specifically, compelling evidence for acidification at sites in the kidney that appear to lack this transporter is presented. In addition, the evidence for the presence in the kidney of a gastric-type H(+)-K+ ATPase is also reviewed. The evidence appears to be strong for a K(+)-stimulated ATPase that is sensitive to omeprazole and SCH 28080, the prototypical H(+)-K+ ATPase inhibitors; however, uncertainties remain because of problems of transport inhibition specificity and discordant results of molecular biologic studies.
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PMID:Proton ATPases and urinary acidification. 787 48

Renal epithelia express at least two distinct urea transporter mRNAs, termed UT1 and UT2, that are derived from a single UT gene by alternative splicing. Previous immunolocalization studies using a polyclonal antibody that does not distinguish between the protein products of these two transcripts revealed that expression of urea transporter protein is restricted to inner medullary collecting ducts and descending thin limbs of Henle's loop. To identify which transcripts account for protein expression in these two structures, we carried out reverse transcription-polymerase chain reaction studies in microdissected structures using UT1- and UT2-specific primers. UT1 mRNA was detected only in the inner medullary collecting duct, consistent with its identification as the vasopressin-regulated urea transporter. In contrast, UT2-mRNA was detected in the late part of descending thin limbs of short loops of Henle and in the inner medullary part of descending thin limbs of long loops of Henle. This localization is consistent with the predicted role of UT2 in medullary urea recycling. Thus, in conjunction with foregoing physiological studies, our data indicate that these transporters play central roles in the urinary concentrating mechanism.
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PMID:Segmental localization of urea transporter mRNAs in rat kidney. 917 77

To test the hypothesis that the abundance of the apical urea transporter of the inner medullary collecting duct (IMCD) is regulated in vivo by factors associated with altered water balance, immunoblots of rat inner medullary membrane fractions were probed with rabbit polyclonal antibodies against the renal urea transporter (RUT) gene product. In inner medullas of Brattleboro rats, which manifest severe chronic water diuresis, a 117-kD band was seen, in addition to the previously described 97-kD band. These two bands were detectable by antibodies directed against two different regions of the RUT sequence. When Brattleboro rats were treated with a 5-d infusion of arginine vasopressin (AVP) by osmotic minipump, the 117-kD band was markedly diminished, whereas the 97-kD band was unchanged. Simultaneous infusion of the diuretic agent furosemide prevented the AVP-induced decrease in the 117-kD band. In AVP-infused Sprague Dawley rats, the 117-kD band was barely perceptible. However, when AVP-treated rats were infused with furosemide for 5 d, the 117-kD band was markedly accentuated, whereas the 97-kD band was unchanged. The abundance of the 117-kD RUT protein in the renal papilla was inversely correlated with dietary protein intake. Further immunoblotting studies revealed that the 117-kD protein is heavily expressed in IMCD cells and not in non-collecting duct components of the inner medulla, and is present in low-density microsome fractions from inner medulla. From this study, the following conclusions can be made: (1) The collecting duct urea transporter is present in at least two forms (97 and 117 kD) in the IMCD. (2) The expression level of the 117-kD urea transporter protein is regulated and is inversely correlated with medullary osmolality and urea concentration, but does not correlate with circulating AVP level. (3) Although AVP regulates RUT function on a short-term basis, long-term changes in AVP levels do not increase RUT abundance.
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PMID:Long-term regulation of renal urea transporter protein expression in rat. 959 69

This study tested whether glucocorticoids regulate tubular urea transport. Urea permeability was measured in perfused inner medullary collecting duct (IMCD) subsegments from rats that underwent adrenalectomy, adrenalectomy plus replacement with a physiologic dose of glucocorticoid (dexamethasone), or sham operation. Compared with sham rats, basal urea permeability in terminal IMCD was significantly increased in adrenalectomized rats and reduced in dexamethasone-treated rats. Vasopressin significantly increased urea permeability in all three groups. In contrast, there was no difference in basal or vasopressin-stimulated urea permeability in initial IMCD between the three groups. Next, membrane and vesicle fraction proteins were isolated from inner medullary tip or base and Western analysis was performed by use of an antibody to the rat vasopressin-regulated urea transporter. Vasopressin-regulated urea transporter protein was significantly increased in both membrane and vesicle fractions from the inner medullary tip of adrenalectomized rats. There was no change in vasopressin-regulated urea transporter protein in the inner medullary base, and Northern analysis showed no change in urea transporter mRNA abundance in either inner medullary region. It was concluded that glucocorticoids can downregulate function and expression of the vasopressin-regulated urea transporter in rat terminal IMCD.
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PMID:Glucocorticoids downregulate the vasopressin-regulated urea transporter in rat terminal inner medullary collecting ducts. 1049 79

Multidrug resistance protein 1 (MRP1) is a transporter protein that helps to protect normal cells and tumor cells against the influx of certain xenobiotics. We previously showed that Mrp1 protects against cytotoxic drugs at the testis-blood barrier, the oral epithelium, and the kidney urinary collecting duct tubules. Here, we generated Mrp1/Mdr1a/Mdr1b triple-knockout (TKO) mice, and used them together with Mdr1a/Mdr1b double-knockout (DKO) mice to study the contribution of Mrp1 to the tissue distribution and pharmacokinetics of etoposide. We observed increased toxicity in the TKO mice, which accumulated etoposide in brown adipose tissue, colon, salivary gland, heart, and the female urogenital system. Immunohistochemical staining revealed the presence of Mrp1 in the oviduct, uterus, salivary gland, and choroid plexus (CP) epithelium. To explore the transport function of Mrp1 in the CP epithelium, we used TKO and DKO mice cannulated for cerebrospinal fluid (CSF). We show here that the lack of Mrp1 protein causes etoposide levels to increase about 10-fold in the CSF after intravenous administration of the drug. Our results indicate that Mrp1 helps to limit tissue distribution of certain drugs and contributes to the blood-CSF drug-permeability barrier.
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PMID:Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. 1067 53

Urea plays a critical role in the urine-concentrating mechanism in the inner medulla. Physiologic data provided evidence that urea transport in red blood cells and kidney inner medulla was mediated by specific urea transporter proteins. Molecular approaches during the past decade resulted in the cloning of two gene families for facilitated urea transporters, UT-A and UT-B, encoding several urea transporter cDNA isoforms in humans, rodents, and several nonmammalian species. Polyclonal antibodies have been generated to the cloned urea transporter proteins, and the use of these antibodies in integrative animal studies has resulted in several novel findings, including: (1) the surprising finding that UT-A1 protein abundance and urea transport are increased in the inner medulla during conditions in which urine concentrating ability is reduced; (2) vasopressin increases UT-A1 phosphorylation in rat inner medullary collecting duct; (3) UT-A protein abundance is upregulated in uremia in both liver and heart; and (4) UT-B is expressed in many nonrenal tissues and endothelial cells. This review will summarize the knowledge gained from using molecular approaches to perform integrative studies into urea transporter protein regulation, both in normal animals and in animal models of human diseases, including studies of uremic rats in which urea transporter protein is upregulated in liver and heart.
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PMID:Molecular approaches to urea transporters. 1239 52

Urea plays a key role in the urine-concentrating mechanism. Physiologic and molecular data demonstrate that urea transport in kidney and red blood cells occurs by specific urea transporter proteins. Two gene families for facilitated urea transporters, UT-A and UT-B, and several urea transporter cDNA isoforms have been cloned from human, rat, mouse, and several non-mammalian species. Polyclonal antibodies have been generated to many of the urea transporter proteins, and several novel findings have resulted from their use in integrative animal studies. For example, (a) vasopressin increases the phosphorylation of UT-A1 in rat inner medullary collecting duct; (b) UT-A1 protein abundance is increased in the rat inner medulla during conditions in which urine-concentrating ability is reduced; and (c) urea transporters are expressed in non-renal tissues, and UT-A protein abundance is up-regulated in uremia in both liver and heart. In addition to the facilitated urea transporters, functional evidence exists for active urea transport in the kidney collecting duct. This review summarizes the physiologic evidence for the existence of facilitated and active urea transporters, the molecular biology of the facilitated urea transporter gene families and cDNAs, and integrative studies into urea transporter protein regulation, both in the kidney and in other organs.
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PMID:Mammalian urea transporters. 1252 63

Physiologic data provided evidence for specific urea transporter proteins in red blood cells and kidney inner medulla. During the past decade, molecular approaches resulted in the cloning of several urea transporter cDNA isoforms derived from two gene families: UT-A and UT-B. Polyclonal antibodies were generated to the cloned urea transporter proteins, and their use in integrative animal studies resulted in several novel findings, including: (1) UT-B is the Kidd blood group antigen; (2) UT-B is also expressed in many non-renal tissues and endothelial cells; (3) vasopressin increases UT-A1 phosphorylation in rat inner medullary collecting duct; (4) the surprising finding that UT-A1 protein abundance and urea transport are increased in the inner medulla during conditions in which urine concentrating ability is reduced; and (5) UT-A protein abundance is increased in uremia in both liver and heart. This review will summarize the knowledge gained from studying molecular mechanisms of urea transport and from integrative studies into urea transporter protein regulation.
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PMID:Molecular mechanisms of urea transport. 1257 50

We tested whether the abundance of transport proteins involved in the urinary concentrating mechanism was altered in rats with uncontrolled diabetes mellitus (DM). Rats were injected with streptozotocin and killed 5, 10, 14, or 20 days later. Blood glucose in DM rats was 300-450 mg/dl (control: 70-130 mg/dl). Urine volume increased in DM rats from 41 +/- 7 ml/100 g body wt (BW) at 5 days to 69 +/- 3 ml/100 g BW at 20 days (control: 9 +/- 1). Urine osmolality of DM rats decreased at 5 days DM and remained low at 20 days. UT-A1 urea transporter protein in the inner medullary (IM) tip was 55% of control in 5-day DM rats but increased to 170, 220, and 280% at 10, 14, and 20 days DM, respectively, due to an increase in the 117-kDa glycoprotein form. UT-A1 in the IM base was increased to 325% of control at 5 days DM with no further increase at 20 days. Aquaporin-2 (AQP2) increased to 290% in the IM base at 5 days DM and 150% in the IM tip at 10 days; both showed no further increase at 20 days. NKCC2/BSC1 increased to 240% in outer medulla at 20 days DM, but not at 5 or 10 days. UT-B and ROMK were unchanged at any time point. The increases in UT-A1, AQP2, and NKCC2/BSC1 proteins during uncontrolled DM would tend to limit the loss of fluid and solute during uncontrolled diabetes.
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PMID:Changes in renal medullary transport proteins during uncontrolled diabetes mellitus in rats. 1269 81


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