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)

The high water permeability characteristic of mammalian red cell membranes is now known to be caused by the protein AQP1. This channel freely permits movement of water across the cell membrane, but it is not permeated by other small, uncharged molecules or charged solutes. AQP1 is a tetramer with each subunit containing an aqueous pore likened to an hourglass formed by obversely arranged tandem repeats. Cryoelectron microscopy of reconstituted AQP1 membrane crystals has revealed the three-dimensional structure at 3-6 A. AQP1 is distributed in apical and basolateral membranes of renal proximal tubules and descending thin limbs as well as capillary endothelia. Ten mammalian aquaporins have been identified in water-permeable tissues and fall into two groupings. Orthodox aquaporins are water-selective and include AQP2, a vasopressin-regulated water channel in renal collecting duct, in addition to AQP0, AQP4, and AQP5. Multifunctional aquaglyceroporins AQP3, AQP7, and AQP9 are permeated by water, glycerol, and some other solutes. Aquaporins are being defined in numerous other species including amphibia, insects, plants, and microbials. Members of the aquaporin family are implicated in numerous physiological processes as well as the pathophysiology of a wide range of clinical disorders.
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PMID:Cellular and molecular biology of the aquaporin water channels. 1087 56

Aquaporin-4 (AQP4) is a member of a water-selective channel aquaporin-family and mainly expressed in the several structures of the brain and in the collecting duct of the kidney. Here we show its functional involvement in the water homeostasis of the ischemic brain. The expression of AQP4-mRNA is increased in the peri-infarcted cortex during the observation period ( approximately 7 days) after MCA-occlusion, maximally on day 3. The change corresponds to the generation and resolution of brain edema monitored by MRI. The signals for the mRNA are predominantly observed in glial cells in the molecular and outer granular layer of the peri-infarcted cortex. These results indicate that AQP4 plays a role in post-ischemic edema formation.
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PMID:Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat. 1089 92

The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9 +/- 0.3 ml/24 h and 2,511 +/- 54 mosmol/kgH(2)O in adult rats and 12.8 +/- 0.8 ml/24 h and 1,042 +/- 44 mosmol/kgH(2)O in senescent animals. Vasopressin V(2) receptor mRNA did not significantly differ between 10 and 30 mo, and [(3)H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3) expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.
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PMID:Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2) vasopressin receptor. 1089 96

In the renal collecting duct, vasopressin increases osmotic water permeability (P(f)) by triggering trafficking of aquaporin-2 vesicles to the apical plasma membrane. We investigated the role of vasopressin-induced intracellular Ca(2+) mobilization in this process. In isolated inner medullary collecting ducts (IMCDs), vasopressin (0.1 nm) and 8-(4-chlorophenylthio)-cAMP (0.1 mm) elicited marked increases in [Ca(2+)](i) (fluo-4). Vasopressin-induced Ca(2+) mobilization was completely blocked by preloading with the Ca(2+) chelator BAPTA. In parallel experiments, BAPTA completely blocked the vasopressin-induced increase in P(f) without affecting adenosine 3',5'-cyclic monophosphate (cAMP) production. Previously, we demonstrated the lack of activation of the phosphoinositide-signaling pathway by vasopressin in IMCD, suggesting an inositol 1,4,5-trisphosphate-independent mechanism of Ca(2+) release. Evidence for expression of the type 1 ryanodine receptor (RyR1) in IMCD was obtained by immunofluorescence, immunoblotting, and reverse transcription-polymerase chain reaction. Ryanodine (100 microm), a ryanodine receptor antagonist, blocked the arginine vasopressin-mediated increase in P(f) and blocked vasopressin-stimulated redistribution of aquaporin-2 to the plasma membrane domain in primary cultures of IMCD cells, as assessed by immunofluorescence immunocytochemistry. Calmodulin inhibitors (W7 and trifluoperazine) blocked the P(f) response to vasopressin and the vasopressin-stimulated redistribution of aquaporin-2. The results suggest that Ca(2+) release from ryanodine-sensitive stores plays an essential role in vasopressin-mediated aquaporin-2 trafficking via a calmodulin-dependent mechanism.
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PMID:Regulation of aquaporin-2 trafficking by vasopressin in the renal collecting duct. Roles of ryanodine-sensitive Ca2+ stores and calmodulin. 1097 64

The phenotype analysis of transgenic mice deficient in specific aquaporin water channels has provided new insights into the role of aquaporins in organ physiology. AQP1-deficient mice are polyuric and are unable to concentrate their urine in response to water deprivation or vasopressin administration. AQP1 deletion reduces osmotic water permeability in the proximal tubule, thin descending limb of Henle and vasa recta, resulting in defective proximal tubule fluid absorption and medullary countercurrent exchange. Mice lacking AQP3, a basolateral membrane water channel expressed mainly in the cortical collecting duct, are remarkably polyuric but are able to generate a partly concentrated urine after water deprivation. In contrast, mice lacking AQP4, a water channel expressed mainly in the inner medullary collecting duct, manifest only a mild defect in maximum urinary concentrating ability. These data, together with phenotype analyses of the brain, lung, salivary gland, and gastrointestinal organs, support the paradigm that aquaporins can facilitate near-isosmolar transepithelial fluid absorption/secretion as well as rapid vectorial water movement driven by osmotic gradients. The phenotype data obtained from aquaporin knockout mice suggest the utility of aquaporin blockers as novel diuretic agents.
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PMID:Physiological importance of aquaporins: lessons from knockout mice. 1099 Mar 71

Vasopressin V2-receptor antagonists are promising agents for the use in water-retaining diseases. Potential renal mechanisms of action include effects on water permeability in the collecting duct as well as on electrolyte transport in the thick ascending limb of Henle's loop (TALH). To elucidate sites of action upstream of the distal tubule, e.g., in TALH, micropuncture experiments were performed in anesthetized rats during application of the V2-receptor antagonist SR 121463B. As compared to vehicle-treated rats, SR 121463B (0.3 mg/kg i.v.) did not affect mean arterial blood pressure (means +/- SEM, n=10 rats per group: 108+/-4 mmHg vs. 107+/-4 mmHg), whole kidney GFR (1.1+/-0.1 ml/min vs. 1.1+/-0.1 ml/min), or whole kidney fractional reabsorption (FR) of potassium (66+/-5% vs. 68+/-4%). The drug, however, reduced whole kidney FR of fluid (92+/-1% vs. 99+/-1%), increased urinary flow rate (84+/-7 microl/min vs. 8+/-1 microl/min) and electrolyte-free-water clearance (72+/-8 microl/min vs. 2+/-1 microl/min), and reduced urinary osmolality (148+/-11 mosmol/kg vs. 1,200+/-185 mosmol/kg). This pronounced diuretic response was associated with a minor reduction in whole kidney FR of sodium (99.6+/-0.1% vs. 99.9+/-0.1%) and chloride (98.3+/-0.2% vs. 98.9+/-0.1%). As compared to vehicle application, SR 121463B did not significantly alter single nephron GFR (39+/-2 nl/min vs. 39+/-1 nl/min, n=22 and 23 nephrons, respectively) or the FR up to the early distal tubule of fluid (76+/-2% vs. 76+/-1%), sodium (92+/-1% vs. 93+/-1%), potassium (91+/-1% vs. 90+/-1%) or chloride (90+/-1% vs. 91+/-1%). Together these data indicate a predominant aquaretic effect of SR 121463B which is located downstream of the early distal tubule. This response is compatible with blockade of vasopressin V2-receptors in the collecting duct and, as directly demonstrated by immunohistochemistry, subsequent retrieval of aquaporin-2 from apical plasma membrane, which inhibits water permeability and transport.
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PMID:Acute renal response to the non-peptide vasopressin V2-receptor antagonist SR 121463B in anesthetized rats. 1099 21

The identification of the first water channel in 1991 opened up a new field in cell biology and physiology that significantly increased our understanding of mammalian water balance regulation. Since then, nine other mammalian aquaporins have been identified. Although the physiological significance of many aquaporins is still to be elucidated, it has been clearly established for aquaporin-2. This water channel, which is expressed in the renal collecting duct, is redistributed to the apical membrane in response to a intracellular signaling cascade, initiated by binding of the antidiuretic hormone vasopressin to its receptor. In pathological conditions, characterized by a reduced reabsorption of water from urine, the expression of aquaporin-2 and the apical targeting is always found to be reduced or absent. Naturally-occurring AQP2 mutations that cause Nephrogenic Diabetes Insipidus, a disease in which the kidney is unable to concentrate urine in response to vasopressin, are extreme examples of this condition. In contrast, in diseases with increased renal water uptake, total and apical membrane expression of aquaporin-2 is increased. Since most aquaporins, including aquaporin-2, are considered to be constitutively open channels, much attention has been given to the regulation of the shuttling of aquaporin-2 to the apical membrane. This review focusses on the present understanding of the regulation of the routing of aquaporin-2 in collecting duct cells and the misrouting of aquaporin-2 mutants in Nephrogenic Diabetes Insipidus.
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PMID:Routing of the aquaporin-2 water channel in health and disease. 1100 88

Hereditary non-X-linked nephrogenic diabetes insipidus (NDI) is caused by mutations in the aquaporin-2 (AQP2) water channel. In transfected cells, the human disease-causing mutant AQP2-T126M is retained at the endoplasmic reticulum (ER) where it is functional and targetable to the plasma membrane with chemical chaperones. A mouse knock-in model of NDI was generated by targeted gene replacement using a Cre-loxP strategy. Along with T126M, mutations H122S, N124S, and A125T were introduced to preserve the consensus sequence for N-linked glycosylation found in human AQP2. Breeding of heterozygous mice yielded the expected Mendelian distribution with 26 homozygous mutant offspring of 99 live births. The mutant mice appeared normal at 2-3 days after birth but failed to thrive and generally died by day 6 if not given supplemental fluid. Urine/serum analysis showed a urinary concentrating defect with serum hyperosmolality and low urine osmolality that was not increased by a V2 vasopressin agonist. Northern blot analysis showed up-regulated AQP2-T126M transcripts of identical size to wild-type AQP2. Immunoblots showed complex glycosylation of wild-type AQP2 but mainly endoglycosidase H-sensitive core glycosylation of AQP2-T126M indicating ER-retention. Biochemical analysis revealed that the AQP2-T126M protein was resistant to detergent solubilization. Kidneys from mutant mice showed collecting duct dilatation, papillary atrophy, and unexpectedly, some plasma membrane AQP2 staining. The severe phenotype of the AQP2 mutant mice compared with that of mice lacking kidney water channels AQP1, AQP3, and AQP4 indicates a critical role for AQP2 in neonatal renal function in mice. Our results establish a mouse model of human autosomal NDI and provide the first in vivo biochemical data on a disease-causing AQP2 mutant.
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PMID:Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus. 1103 38

This study was carried out to investigate the role of aquaporin (AQP) in the peritoneum undergoing continuous ambulatory peritoneal dialysis (CAPD). Furthermore, we examined the effects of treatment with prednisolone (PSL) in a rat model of peritoneal sclerosis. We modelled peritoneal sclerosis by using dialysis solution with the addition of 0.1% chlorhexidine gluconate (CHG) for 10 days. Twenty male Wistar Kyoto (WKY) rats were divided into four groups and dialyzed with various solutions: (1) saline (NS group, n = 5); (2) 10% glucose (TZ group, n = 5); (3) 0.1% CHG (CHG group, n = 5); and (4) 0.1% CHG plus PSL (CHG + PSL group, n = 5). Expression of mRNA of AQPs (AQP-1-AQP-4) was studied by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR). Expression of AQP-4 was also measured by Western blot analysis. Ultrafiltration volume and peritoneal function were measured by the peritoneal equilibration test. In the TZ group, expression of AQP-1 and AQP-4 were significantly enhanced, in parallel with an increment in ultrafiltration volume. On the other hand, in the CHG group, expression of AQP-1 and AQP-4 were significantly suppressed, and ultrafiltration volume was lost. The use of PSL with CHG completely restored the expression of AQP-1 and AQP-4, and peritoneal function improved. No expression of AQP-2 and AQP-3 was seen in the peritoneum. Our results suggest that AQP-1 and AQP-4 may be important factors in water transport in patients undergoing CAPD. PSL might be an effective treatment to prevent the progress of peritoneal sclerosis in patients undergoing CAPD.
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PMID:Glucocorticoid restores the deterioration of water transport in the peritoneum through increment in aquaporin. 1104 15

The renal connecting tubule (CNT) is a distinct segment that occurs between the distal convoluted tubule (DCT) and the cortical collecting duct. On the basis of its characterization in rabbit it is widely believed that connecting tubule cells have a low permeability to water and do not respond to vasopressin. Here we utilize segment-specific markers and specific aquaporin antibodies to characterize expression of water channels in CNT of the rat by immunocytochemistry. Colocalization of aquaporin 2 (AQP2), AQP3, and AQP4 with Na(+), Ca(2+) exchanger (NCX), a transporter characteristic of the connecting tubule, gave heterogeneous labeling. There was aquaporin labeling in many but not all regions labeled by NCX. Colocalization of AQP2 with AQP3 and with AQP4 showed that AQP3 and AQP4 labeling were always accompanied by AQP2. Immunogold labeling and electron microscopy showed that NCX-labeled cells with AQP2 labeling had the morphology of CNT cells, whereas NCX-labeled cells without AQP2 labeling were DCT cells. The latter regions were identified as the late region of the DCT known as DCT2. Additionally, regions of CNT lacking AQP2 labeling could be identified in Brattleboro rats not treated with vasopressin but not in such animals chronically treated with deamino-Cys(1),D-Arg(8)-vasopressin (dDAVP). Quantitative analysis of labeling was consistent with expression of AQP2 over a longer region of CNT after dDAVP exposure.
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PMID:Expression of aquaporins in the renal connecting tubule. 1105 48


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