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)

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the inability of the kidney to concentrate urine in response to vasopressin (AVP). Following the recent characterization of the cDNA and genomics sequences encoding the human V2 receptor to AVP (AVPR2), X-linked NDI has been found to be due to mutations in the AVPR2 gene that maps to the chromosome Xq28 region. To date more than 30 mutations, insertions or deletions have been reported in independent families, without any significant differences in the phenotypic expression of the disease. The AVPR2 is a member of the superfamily of 7 transmembrane domain, G protein-coupled receptor, linked to cyclic AMP second messenger system. Other types of inheritance have been described in NDI, and recently, a mutation of the aquaporin-2 gene, encoding a water channel of the renal collecting duct, has been reported in an autosomal recessive form of NDI.
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PMID:[Hereditary nephrogenic diabetes insipidus]. 764 Jul 59

The sites of water transport along the nephron are well characterized, but the molecular basis of renal water transport remains poorly understood. CHIP28 is a 28-kD integral protein which was proposed to mediate transmembrane water movement in red cells and kidney (Preston, G. M., T. P. Carroll, W. B. Guggino, and P. Agre. 1992. Science [Wash. DC]. 256:385-387). To determine whether CHIP28 could account for renal epithelial water transport, we used specific polyclonal antibodies to quantitate and localize CHIP28 at cellular and subcellular levels in rat kidney using light and electron microscopy. CHIP28 comprised 3.8% of isolated proximal tubule brush border protein. Except for the first few cells of the S1 segment, CHIP28 was immunolocalized throughout the convoluted and straight proximal tubules where it was observed in the microvilli of the apical brush border and in basolateral membranes. Very little CHIP28 was detected in endocytic vesicles or other intracellular structures in proximal tubules. Uninterrupted, heavy immunostaining of CHIP28 was also observed over both apical and basolateral membranes of descending thin limbs, including both short and long loops of Henle. These nephron sites have constitutively high osmotic water permeabilities. CHIP28 was not detected in ascending thin limbs, thick ascending limbs, or distal tubules, which are highly impermeable to water. Moreover, CHIP28 was not detected in collecting duct epithelia, where water permeability is regulated by antidiuretic hormone. These determinations of abundance and structural organization provide evidence that the CHIP28 water channel is the predominant pathway for constitutive transepithelial water transport in the proximal tubule and descending limb of Henle's loop.
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PMID:CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. 767 19

The tissue distribution of mRNA encoding rat kidney water channel CHIP28k was determined by in situ hybridization. cDNA encoding rat kidney CHIP28k was isolated by homology to human erythrocyte CHIP28 (G. M. Preston and P. Agre. Proc. Natl. Acad. Sci. USA 88: 11110-11114, 1991) and used to construct 155-base 35S-labeled cRNA sense and antisense probes corresponding to base pair 7-162. Fixed and frozen tissues were cut in 6- to 12- microns sections, hybridized with probes at 55 degrees C for 16 h, and exposed for 5-9 days. In renal cortex, CHIP28k mRNA was detected intensely on proximal tubule epithelial cells but not in glomeruli or collecting duct. Hybridization to proximal tubule was strongest in deep renal cortex. In no study was there significant hybridization of sense cRNA probe. In renal papilla, CHIP28k mRNA was detected in only a fraction of tubules corresponding to thin limbs of Henle. Hybridization in spleen was observed in red splenic pulp containing erythroid precursors but not in white pulp. In colon, there was selective hybridization in crypt epithelial cells but not in villus epithelial cells or nonepithelial structures. In lung, hybridization was observed in alveolar epithelial cells. In eye, there was selective hybridization in corneal endothelium and ciliary body. No hybridization was observed in any cell types in liver. Northern analysis revealed a 2.8-kilobase mRNA encoding CHIP28k in kidney cortex and papilla but not in brain, skeletal muscle, and liver. These results indicate a wide and highly selective tissue distribution of mRNA encoding the CHIP28k water channel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-specific expression of mRNA encoding rat kidney water channel CHIP28k by in situ hybridization. 767 51

In searching for a basolateral membrane water transporter in rat kidney with homology to channel forming integral protein (CHIP28), water channel-collecting duct (WCH-CD), and mercurial-insensitive water channel (MIWC), we cloned a new member of the major intrinsic protein family (GLIP, GLycerol Intrinsic Protein). GLIP cDNA had an 855-base pair open reading frame encoding a 30.5-kDa protein with 19-23% amino acid identity to the water channels and 36% identity to the bacterial glycerol facilitator GlpF. Northern blot analysis showed a 5.5-kilobase mRNA encoding GLIP in kidney, brain, and lung; RT-PCR/Southern blot analysis indicated expression of GLIP in kidney, brain, lung, eye, colon, stomach, and skeletal muscle, but not in heart, liver, and spleen. In situ hybridization in rat kidney showed GLIP mRNA expression in medullary collecting duct. Immunofluorescence with a peptide-derived polyclonal antibody showed GLIP protein expression in basolateral membrane of kidney collecting duct principal cells and brain meningeal cells. Functional measurements in Xenopus oocytes expressing GLIP cRNA showed a > 20-fold increase in [3H]glycerol uptake compared with water-injected oocytes; glycerol uptake was inhibited 88% by diisothiocyanodisulfonic stilbene (0.2 mM) and 36% by phloretin (0.25 mM). GLIP did not function as a transporter for water, urea, inositol, glucose, lactate, and monovalent ions. Glycerol uptake in oocytes expressing CHIP28 and MIWC was not different from that in water-injected controls. GLIP represents the first mammalian water channel homolog that selectively transports a solute other than water. The physiological substrate(s) and role(s) of GLIP remain to be elucidated.
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PMID:Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. 806 28

Human urine can be concentrated up to four times higher than that of the plasma. Urine concentrating mechanism has attracted for a long time. However, studies in the field are now picking up momentum due to recent breakthrough discoveries using molecular biology techniques. Vasopressin-regulated water channel in the apical membrane of the collecting duct and water channel in the basolateral side of the membrane were cloned. cloned. Osmolality-dependent chloride channel in the thin ascending limb of Henle was also cloned. In addition, vasopressin-regulated urea transporter was found in the collecting duct. These newly discovered channels and transporter should be playing important physiological roles in urine concentrating mechanism. Furthermore, recent findings on osmolytes and their transporters also add to the list of urine concentrating mechanisms.
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PMID:[A study of urine concentrating mechanism--a molecular biological approach]. 807 15

The plasma membrane composition of virtually all eukaryotic cells is maintained and continually modified by the recycling of specific protein and lipid components. In the kidney collecting duct, urinary acidification and urinary concentration are physiologically regulated at the cellular level by the shuttling of proton pumps and water channels between intracellular vesicles and the plasma membrane of highly specialized cell types. In the intercalated cell, hydrogen ion secretion into the urine is modulated by the recycling of vesicles carrying a proton pumping ATPase to and from the plasma membrane. In the principal cell, the antidiuretic hormone, vasopressin, induces the insertion of vesicles that contain proteinaceous water channels into the apical cell membrane, thus increasing the permeability to water of the epithelial layer. In both cell types, 'coated' carrier vesicles are involved in this process, but whereas clathrin-coated vesicles are involved in the endocytotic phase of water channel recycling, the transporting vesicles in intercalated cells are coated with the cytoplasmic domains of the proton pumping ATPase. By a combination of morphological and functional techniques using FITC-dextran as an endosomal marker, we have shown that recycling endosomes from intercalated cells are acidifying vesicles but that they do not contain water channels. In contrast, principal cell vesicles that recycle water channels do not acidify their lumens in response to ATP. These non-acidic vesicles lack functionally important subunits of the vacuolar proton ATPase, including the 16 kDa proteolipid that forms the transmembrane proton pore. Because these endosomes are directly derived via clathrin-mediated endocytosis, our results indicate that endocytotic clathrin-coated vesicles are non-acidic compartments in principal cells. In contrast, recycling vesicles in intercalated cells contain large numbers of proton pumps, arranged in hexagonally packed arrays on the vesicle membrane. These pumps are inserted into the apical plasma membrane of A-type (acid-secreting) intercalated cells, and the basolateral plasma membrane of B-type (bicarbonate-secreting) cells in the collecting duct. Both apical and basolateral targeting of H(+)-ATPase-containing vesicles in these cells may be directed by microtubules, because polarized insertion of the pump into both membrane domains is disrupted by microtubule depolymerizing agents. However, the basolateral localization of other transporting proteins in intercalated cells, including the band 3-like anion exchanger and facilitated glucose transporters, is not affected by microtubule disruption.
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PMID:Endosomal pathways for water channel and proton pump recycling in kidney epithelial cells. 814 5

The effect of insulin on water and urea transport was examined in normal isolated rat inner medullary collecting duct (IMCD). Hydraulic conductivity (Lp, x 10(-6) cm.atm-1.s-1), diffusional water permeability (Pdw, x 10(-5) cm/s) and [14C]urea permeability (x 10(-5) cm/s) were studied at 37 degrees C and pH 7.4. Insulin (6 x 10(-8) M; 200 microU/ml) added to the bath fluid enhanced Lp from 0.40 +/- 0.10 to 1.21 +/- 1.40 (P < 0.01) and Pdw from 42.40 +/- 3.40 to 58.50 +/- 5.00 (P < 0.02) and also stimulated Lp in a dose-dependent manner. In the presence of antidiuretic hormone (ADH)-stimulated Pdw (10 microU/ml), insulin increased Pdw even more. Prostaglandin E2 (10(-5) M) added to the bath reversibly increased insulin-induced Lp. Forskolin (10(-4) M) blocked the action of insulin. Colchicine (10(-4) M) and V1-receptor antagonist (10(-4) M) inhibited the development but not the maintenance of insulin-stimulated Pdw. Vanadate (2.5 x 10(-6) M) enhanced Pdw. Polymyxin B (10(-5) M) inhibited the insulin-stimulated Pdw, whereas in a glucose-free medium insulin did not enhance Pdw. Urea transport was not affected by insulin. These data suggest that insulin may enhance water transport, probably by stimulating glucose transporters, which would serve as a water channel. We cannot rule out the possibility that insulin may be eliciting existing ADH-like mechanisms of water transport, beyond the microtubule step, to establish water transport.
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PMID:Effect of insulin on water and urea transport in the inner medullary collecting duct. 816 Jul 87

Antidiuretic hormone (ADH) stimulation of renal epithelial cells elicits a large increase in apical membrane osmotic water permeability (Pf) produced by the fusion of water channel containing vesicles with the apical membrane. Removal of ADH stimulation results in retrieval of apical water channels into a specialized non-acidic endosomal compartment. Previous studies (Sabolic, I., Wuarin, F., and Shi, L. B. (1992) J. Cell Biol. 119, 111-122) have shown that water channel containing papillary endosomes labeled with fluorescein-dextran can be isolated from rat renal papilla. We have utilized small particle flow sorting methodology to both monitor and improve upon the purification of these water channel containing endosomes (WCV). Flow cytometry analysis on a vesicle-by-vesicle basis demonstrates that WCV are homogeneous with respect to entrapped fluorescein-dextran, the apical membrane enzyme marker leucine amino peptidase and ultrastructural morphology. WCV do not acidify their luminal contents after addition of Mg-ATP but contain abundant functional water channels (Pf0.28 cm/s at 23 degrees C) as determined by stopped flow fluorimetry. SDS-polyacrylamide gel electrophoresis analysis shows that purified WCV are composed of 20 major protein bands. To determine the identity of WCV water channels, WCV proteins were probed with affinity purified antisera recognizing two renal water channel proteins. These include Aquaporin-CHIP found in the proximal tubule and thin descending limb of Henle and the candidate ADH water channel protein WCH-1 or Aquaporin- (AQP) CD present in the ADH-responsive epithelial cells of the collecting duct. These data reveal that WCV contained little or no AQP-CHIP protein. In contrast, WCV are highly enriched for AQP-CD protein. Together, these data define the protein composition of the papillary WCV and link directly the presence of functional apical membrane water channels with the presence of the AQP-CD protein.
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PMID:Characterization of purified endosomes containing the antidiuretic hormone-sensitive water channel from rat renal papilla. 816 2

In amphibian bladder, arginine vasopressin (AVP) depolymerizes F-actin in the apical region of the granular cell, promoting fusion of water channel-carrying vesicles with the apical membrane. We now report the effect of AVP on F-actin in the mid- and terminal segments of rat inner medullary collecting duct (IMCD2 and IMCD3). In IMCD3, 5 min of stimulation by 2.5-250 nM AVP significantly depolymerized F-actin by 13-24% in whole cell assays employing the rhodamine-phalloidin binding technique. The IMCD2 was more sensitive, responding to subnanomolar (0.25 nM) AVP with 6 +/- 2% depolymerization. Depolymerization occurred as early as 2 min after 2.5 and 25 nM but not 250 nM AVP. 8-Bromoadenosine 3',5'-cyclic monophosphate depolymerized F-actin in IMCD3 at both 2 and 5 min. Immunogold labeling of the apical actin pool in IMCD3 principal cells was reduced by 26 +/- 5% (P < 0.05) by 2.5 nM AVP; the lateral and basal pools showed no significant changes. Capillary endothelial, thin limb of Henle, and intercalated cells showed no changes in immunogold labeling after AVP. Thus reorganization of the apical actin network by AVP is a consistent finding in both mammalian and amphibian target cells.
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PMID:Vasopressin depolymerizes apical F-actin in rat inner medullary collecting duct. 821 31

Vasopressin (antidiuretic hormone) regulates body water balance by controlling water permeability of the renal collecting ducts. The control mechanisms may involve alterations in the number or unit conductance of water channels in the apical plasma membrane of collecting-duct cells. How this occurs is unknown, but indirect evidence exists for the "shuttle" hypothesis, which states that vasopressin causes exocytic insertion of water channel-laden vesicles from the apical cytosol. To test key aspects of the shuttle hypothesis, we have prepared polyclonal antisera against the recently cloned collecting-duct water channel protein and used the antisera in immunolocalization studies (light and electron microscopic levels) in thin and ultrathin cryosections from rat kidney. Labeling was seen exclusively in collecting-duct principal cells and inner medullary collecting-duct cells. Apical membrane labeling was intense. There was heavy labeling of abundant small subapical vesicles and of membrane structures within multivesicular bodies. In addition, labeling of basolateral plasma membranes in inner medullary collecting ducts was present. Depriving rats of water for 24 or 48 hr markedly increased collecting-duct water-channel protein expression determined by immunoblotting and immunolabeling. These results are compatible with at least two complementary modes of water-channel regulation in collecting-duct cells: (i) control of channel distribution between the apical membrane and a reservoir in subapical vesicles (shuttle hypothesis) and (ii) regulation of the absolute level of expression of water-channel protein.
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PMID:Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. 826 5


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