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)

To evaluate the functional role of GATA motifs in the 5'-flanking region of a kidney-specific AQP-2 water channel gene, we sought to isolate a GATA factor(s) expressed in collecting ducts and determined the role on the AQP-2 promoter. Two cDNAs encoding GATA factors were isolated from rat kidney, whose sequences were highly homologous with human GATA-2 and -3. Reverse-transcription PCR using dissected nephron segments revealed that rat GATA-3 but not GATA-2 was expressed in collecting ducts, thus indicating that GATA-3 could interact with GATA motifs in the AQP-2 promoter. Transactivation experiments utilizing the rat GATA-3 expression vector indicated that rat GATA-3 increased the AQP-2 promoter activity about fourfold. These results indicated that GATA motifs in the 5'-flanking region of the hAQP-2 gene were functional cis-elements and that GATA-3 in collecting ducts may be one of the important regulators of AQP-2 expression in vivo.
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PMID:Regulation of aquaporin-2 gene transcription by GATA-3. off. 912 53

Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.
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PMID:Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. 914 44

We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 +/- 3.4 vs. 4.1 +/- 0.3 mmHg, and reduced plasma sodium concentrations (142.2 +/- 1. 6 vs. 149.1 +/- 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 +/- 53%, n = 12) relative to sham-operated controls (100 +/- 13%, n = 14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective. Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 +/- 28% of sham levels, n = 6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF.
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PMID:Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct. 914 58

Aquaporin-2 (AQP-2) water channel is a key molecule for urinary concentration whose expression is augmented by dehydration in vivo. To elucidate the regulatory mechanism of this phenomenon in vitro, mouse collecting duct cell lines were established from a transgenic mouse harboring temperature-sensitive simian virus 40 large T antigen gene and then screened for the AQP-2 expression, using ribonuclease protection assay. In one cell line designated C4, the endogenous AQP-2 mRNA level measured by ribonuclease protection assay increased fourfold after treatment with chlorophenylthio-cAMP (cpt-cAMP) (400 microM). In contrast, phorbol 12-myristate 13-acetate did not affect the AQP-2 mRNA level. To identify the molecular mechanism(s) of cAMP-induced upregulation of AQP-2 mRNA in C4 cells, luciferase assay was performed using various 5'-flanking regions of the human AQP-2 gene. Luciferase activity in C4 cells transfected with constructs containing approximately 2.8-kbp or 224-bp 5'-flanking region showed a 3.5-fold increase by cpt-cAMP treatment, indicating that the 224-bp 5'-flanking region contains the elements necessary for cAMP-induced regulatory mechanisms. This region contains cAMP-responsive element (CRE), and the deletion of the core sequence of CRE (GACGTCA) or introduction of mutation into CRE (GTGGTCA) completely abolished the responsiveness to cpt-cAMP, confirming the key role of CRE in the cAMP-induced transcriptional activation of the AQP-2 gene. Electrophoretic mobility shift assay revealed the existence of proteins binding to CRE in C4 cells and in rat kidney. The binding of CRE proteins to CRE was increased in the nuclear extract from cpt-cAMP-treated C4 cells and dehydrated rat kidney compared with those from controls. These results demonstrated that the CRE in the AQP-2 gene promoter is a key cis-element for cAMP-mediated transcriptional regulation of this gene and may be important for in vivo regulation of AQP-2 expression in a dehydrated state.
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PMID:Transcriptional regulation of aquaporin-2 water channel gene by cAMP. 918 51

Like mammalian kidney collecting duct, the water permeability of frog urinary bladder epithelial cells is antidiuretic hormone (ADH)-sensitive. In kidney, this permeability is mediated by water channels named aquaporins. We recently reported the cloning of the frog aquaporin CHIP (FA-CHIP), a water channel from frog urinary bladder. FA-CHIP has 79% identity with rat Aquaporin 1 (AQP1) and only 42% identity with the kidney collecting duct Aquaporin 2 (AQP2). The purpose of this study was to examine the localization of FA-CHIP in frog urinary bladder. We raised antibodies against peptides of 15 to 17 residues, encompassing the N-ter and C-ter regions of FA-CHIP. Anti-FA-CHIP antibodies were used for Western blotting, indirect immunofluorescence microscopy and gold labeling electron microscopy in urinary bladder and other frog tissues. By Western blotting of frog urinary bladder total homogenate, the antibodies recognized a band of 29 kDa and glycosylated forms of the protein between 40 and 70 kDa. No signal was found on membrane preparations from epithelial cell homogenate. FA-CHIP was also found in frog skin, brain, gall bladder, and lung. In immunofluorescence microscopy on urinary bladder sections, FA-CHIP was localized to endothelial cells of blood capillaries and on mesothelial cells of the serosal face. Red blood cells, epithelial and basal cells were unstained. The localization of FA-CHIP in cell plasma membranes was confirmed by gold labeling electron microscopy. In other positive tissues, FA-CHIP was also localized to capillaries. In brain, plasma membranes of epithelial cells were also stained. In conclusion, like its mammalian homologue AQP1, FA-CHIP appears to be localized to constitutively water permeable cells of frog. Therefore, it belongs to the AQP1 family of proteins although unlike AQP1, FA-CHIP is absent from red blood cells and kidney. In frog urinary bladder and skin, FA-CHIP probably plays an important role in water transport across the barriers in series with the ADH-sensitive epithelial cells.
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PMID:Localization of the FA-CHIP water channel in frog urinary bladder. 924 82

Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renal collecting duct. The aquaporin-2 water channel has been demonstrated to be the target for this action of vasopressin. Recent studies have demonstrated that vasopressin, acting through cyclic AMP, triggers fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principal cells. The vesicle-targeting proteins synaptobrevin-2 and syntaxin-4 are proposed to play roles in this process.
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PMID:Regulation of aquaporin-2 water channel trafficking by vasopressin. 926 Oct 56

The aquaporins are a recently recognized family of water channels that mediate water transport in kidney and in other organs. Aquaporin-2, 'vasopressin-regulated water channel', is regulated by vasopressin in two ways to account for overall control of collecting duct water permeability. First, vasopressin has a short-term effect in triggering translocation of aquaporin-2-containing intracytoplasmic vesicles to the apical plasma membrane, thus increasing principal cell water permeability. Second, vasopressin has a long-term effect in increasing the abundance of aquaporin-2 in collecting duct principal cells, increasing the maximal attainable water permeability. Using animal models, defects in these control mechanisms have been shown to be associated with several disorders of water balance, including central diabetes insipidus, congenital nephrogenic diabetes insipidus, acquired diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, and several extracellular fluid volume expanded states.
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PMID:Role of aquaporins in water balance disorders. 926 86

Freeze-fracture electron microscopy (FFEM) of kidney collecting duct, muscle, astrocytes in brain, and other mammalian tissues has revealed regular square arrays of intramembrane particles called orthogonal arrays of particles (OAPs). Their possible role in membrane structure and transport have been proposed, and their absence or decrease has been noted in a variety of hereditary and acquired diseases. A transgenic mouse lacking water channel AQP4 was used to show that AQP4 is the OAP protein. FFEM was done on kidney, skeletal muscle, and brain from AQP4 wild-type [+/+], heterozygous [+/-] and knock-out [-/-] mice. The [-/-] mice did not express detectable AQP4 protein, but were grossly indistinguishable from [+/+] mice. FFEM was done on blinded samples of kidney, brain and muscle from 9 mice. In all 6 kidney samples from [+/+] and [+/-] mice, OAPs similar to those in AQP4-transfected CHO cells were found in basolateral membranes of collecting duct principal cells. In all muscle and brain samples from [+/+] and [+/-] mice, OAPs of identical ultrastructure to those in kidney were seen, but in smaller patch sizes. OAPs were not seen in any sample from [-/-] mice. Label-fracture analysis using a peptide-derived AQP4 polyclonal antibody showed immunogold labeling of OAPs in AQP4-expressing CHO cells. These studies provide direct evidence that AQP4 is required for formation of OAPs and is a component of OAPs, thus establishing the identity and function of OAPs.
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PMID:Absence of orthogonal arrays in kidney, brain and muscle from transgenic knockout mice lacking water channel aquaporin-4. 942 93

Aquaporins are integral membrane proteins, which function as specialized water channels to facilitate the passage of water through the cell membrane. In mammals six different aquaporins have been identified up to now, four of which (aquaporin-1 to aquaporin-4) are expressed in the kidney. Because of its importance for normal water homeostasis and its involvement in many water balance disorders, aquaporin-2, the predominant vasopressin-regulated water channel of the renal collecting duct, is discussed in detail.
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PMID:Physiology and pathophysiology of the aquaporin-2 water channel. 944 61

Volemia and osmolality homeostasis is ensured in vertebrates through neuroendocrine reflexes, involving an afferent neural branch from baro- and osmo-receptors to hypothalamus and an efferent endocrine branch from secretory neurons to target hydroosmotic cells equipped with receptors and effectors. Whereas the osmoregulatory system in the tadpole comprises three organs, namely gut, kidney and gills, as in freshwater fishes, the adult displays a quaternary strategy with gut, kidney, urinary bladder and skin. In particular, the cutaneous permeability entails a great evaporative water loss when the animal is in the open air, loss that must be compensated by water reabsorption through the nephron and the urinary bladder and mainly by water uptake through the skin. Adaptation occurred at the level of these organs by regulation of their permeability through neurohypophysial hormones. Aside from vasotocin, active on the three organs, all anuran Amphibia possess hydrin 2 (vasotocinyl-Gly), a peptide resulting from a down-regulation of provasotocin processing. Exceptionally Xenopus laevis, a permanent aquatic toad, has hydrin 1 (vasotocinyl-Gly-Lys-Arg) instead of hydrin 2. Hydrins are somewhat more active than vasotocin on water permeation of skin and bladder but are devoid of antidiuretic activity. Adaptive evolution has created, along with the vasotocin-nephron system, preserved in all terrestrial non-mammalian tetrapods, additional functions such as the hydrin-skin and hydrin-bladder rehydration mechanisms. Specific hydrin receptors might exist in the skin and the bladder, different from those of vasotocin in the kidney. It is assumed that the water channel recruitment mechanism, found for vasopressin acting on the collecting duct principal cells in mammals, is also involved when vasotocin and hydrins stimulate their hydroosmotic target cells and that hormone-regulated aquaporin 2-like proteins could be identified in the three osmoregulatory organs of amphibians.
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PMID:Adaptive evolution of water homeostasis regulation in amphibians: vasotocin and hydrins. 946 98


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