Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OREBP (osmotic response element-binding protein), also called TonEBP or NFAT5, is thought to induce the expression of genes that increase the accumulation of organic osmolytes to protect cells against a hypertonic environment. To investigate the consequences of lacking OREBP activity, transgenic (Tg) mice that overexpress OREBPdn (dominant negative form of OREBP) specifically in the epithelial cells of the renal collecting tubules were generated. These mice showed impairment in their urine concentrating mechanism, most likely due to reduced expression of the aquaporin AQP2 and the urea transporter UT-A1 and UT-A2 mRNAs. When deprived of water or after the administration of a vasopressin analogue, urine osmolality of the Tg mice was significantly increased but not to the same extent as that of the wild type mice. The expression of AQP2 and UT-A1, but not UT-A2 mRNAs, was increased to the same level as that of the wild type mice in the water deprivation state, indicating that the vasopressin regulatory mechanism was not affected by OREBPdn. These data indicate that in addition to vasopressin, OREBP is another essential regulator of the urine concentrating mechanism. Furthermore, the OREBPdn Tg mice developed progressive hydronephrosis soon after weaning, confirming the osmoprotective function of OREBP implicated by the in vitro experiments.
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PMID:Osmotic response element-binding protein (OREBP) is an essential regulator of the urine concentrating mechanism. 1534 63

Water permeability of the basolateral membrane was estimated in isolated fragments of OMCD or IMCD in the Wistar rats. Apical surface of the fragments was blocked with oil injected into the lumen. Apparent water permeability coefficient (Pf) was measured by the rate of epithelium swelling following transition from hypertonic to isotonic medium (600 mOsm to 300 mOsm). Water deprivation caused significant increase in the Pf value in OMCD and IMCD fragments. Desmopressin (10(-8) M) increased water permeability in hydrated rats both in OMCD and IMCD. Mercury chloride decreased the Pf and abolished the effect of desmopressin in reversible manner. Estimation of aquaporins 2, 3, 4 mRNA content in the renal medulla was performed by semi-quantitative RT-PCR. Content of AQP4 and AQP2 mRNA in dehydrated animals was significantly higher than in hydrated ones both in outer medulla and inner medulla. Expression of AQP3 increased during dehydration only in the inner medulla. The findings reveal that water permeability of OMCD and IMCD can be increased by physiological stimuli, e.g. water deprivation. The activation of gene expression of the key elements of vasopressin signal system seems to contribute to this reaction.
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PMID:[Water permeability of the OMCD and IMCD cells' basolateral membrane under the conditions of dehydration and dDAVP action]. 1546 10

The present study examined the role of PKA and serine256 (S256) phosphorylation for AQP2 trafficking and recycling using cells transfected with wild-type AQP2 (AQP2-WT) or mutant AQP2 and high-resolution confocal microscopic techniques. In transiently transfected MDCK-C7 cells, stimulation with forskolin induced translocation of AQP2-WT to the plasma membrane. Treatment of AQP2-WT cells with the PKA inhibitor H-89 following forskolin stimulation resulted in internalization of AQP2-WT. Moreover, H-89 treatment of AQP2-S256D (mimicking constitutively phosphorylated AQP2 and hence localized to the plasma membrane) resulted in redistribution of AQP2-S256D to intracellular vesicles, even in the presence of forskolin. Both PGE2 and dopamine stimulation induced endocytosis of AQP2-WT and AQP2-S256D, respectively, in forskolin-stimulated cells. Consistent with this, dopamine in the presence of vasopressin stimulated endocytosis of AQP2 in slices of rat kidney inner medulla without substantial dephosphorylation. In conclusion, these results strongly suggest that 1) S256 phosphorylation is necessary but not sufficient for AQP2 plasma membrane expression, 2) active PKA is required for AQP2 plasma membrane expression, 3) PGE2 and dopamine induce internalization of AQP2 independently of AQP2 dephosphorylation, and 4) preceding activation of cAMP production is necessary for PGE2 and dopamine to cause AQP2 internalization.
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PMID:Bidirectional regulation of AQP2 trafficking and recycling: involvement of AQP2-S256 phosphorylation. 1562 84

The objective of this investigation was to use semi-quantitative immunohistochemistry to determine the distribution and expression levels of AQP2 and AQP3 proteins in normal human Tissue MicroArrays. Expression of the vasopressin regulated AQP2 was observed in a limited number of tissues. AQP2 was prominent in the apical and subapical plasma membranes of cortical and medullary renal collecting ducts. Surprisingly, weak AQP2 immunoreactivity was also noted in pancreatic islets, fallopian tubes and peripheral nerves. AQP2 was also localized to selected parts of the central nervous system (ependymal cell layer, subcortical white matter, hippocampus, spinal cord) and selected cells in the gastrointestinal system (antral and oxyntic gastric mucosa, small intestine and colon). These findings corroborate the restricted tissue distribution of AQP2. AQP3 was strongly expressed in many of the human tissues examined particularly in basolateral membranes of the distal nephron (medullary collecting ducts), distal colon, upper airway epithelia, transitional epithelium of the urinary bladder, tracheal, bronchial and nasopharyngeal epithelium, stratified squamous epithelial cells of the esophagus, and anus. AQP3 was moderately expressed in basolateral membranes of prostatic tubuloalveolar epithelium, pancreatic ducts, uterine endometrium, choroid plexus, articular chondrocytes, subchondral osteoblasts and synovium. Low AQP3 levels were also detected in skeletal muscle, cardiac muscle, gastric pits, seminiferous tubules, lymphoid vessels, salivary and endocrine glands, amniotic membranes, placenta and ovary. The abundance of basolateral AQP3 in epithelial tissues and its expression in many non-epithelial cells suggests that this aquaglyceroporin is a major participant in barrier hydration and water and osmolyte homeostasis in the human body.
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PMID:Distribution of AQP2 and AQP3 water channels in human tissue microarrays. 1570 94

In addition to its effect on water permeability, vasopressin, through its V2 receptors (AVPR2), stimulates Na reabsorption in the collecting duct by increasing the activity of the amiloride-sensitive sodium channel ENaC. This study evaluated whether dDAVP (a potent AVPR2 agonist) reduces sodium excretion in healthy humans (n = 6) and in patients with central (C; n = 2) or nephrogenic (N) diabetes insipidus (DI) as a result of mutations of either the aquaporin 2 gene (AQP2; n = 3) or AVPR2 (n = 10). dDAVP was infused intravenously (0.3 microg/kg body wt in 20 min), and urine was collected for 60 min before (basal) and 150 min after the infusion. dDAVP markedly reduced both urine flow rate and sodium excretion in healthy individuals. A reduction in sodium excretion was also observed in CDI and NDI-AQP2 patients but not in NDI-AVPR2 patients. The magnitude of the fall in sodium excretion correlated with the rise in urine osmolality and the fall in urine output but not with the simultaneously observed fall in mean BP. These results suggest that the dDAVP-induced antinatriuresis is due to a direct V2 receptor-dependent stimulation of sodium reabsorption in the collecting duct and is not secondary to a hemodynamic effect. In conclusion, this study reveals a potent V2-dependent antinatriuretic effect of vasopressin in humans. The possibility that an inappropriate stimulation of ENaC by vasopressin might lead to significant sodium retention in chronic situations remains to be determined.
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PMID:Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans. 1588 62

The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with l-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HT+T rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V(2) vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.
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PMID:Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism. 1591 74

Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat decreases AVP-induced water flow and releases PGE(2). We observed that dehydration of rats decreases the expression of P2Y2 receptor in inner medulla (IM) and P2Y2-R-mediated PGE(2) release by IMCD. Because circulating vasopressin (AVP) levels are increased in dehydrated condition, we examined whether chronic infusion of desmopressin (dDAVP) has a similar effect on the expression and activity of P2Y2-R. Groups of rats were infused with saline or dDAVP (5 or 20 ng/h sc, 5 or 6 days) via osmotic minipumps and euthanized. Urine volume, osmolality, and PGE(2) metabolite content were determined. AQP2- and P2Y2- and V2-R mRNA and/or protein in IM were quantified by real-time RT-PCR and immunoblotting, respectively. P2Y2-R-mediated PGE(2) release by freshly prepared IMCD was assayed using ATPgammaS as a ligand. Chronic dDAVP infusion resulted in low-output of concentrated urine and significantly increased the AQP2 protein abundance in IM. On the contrary, dDAVP infusion at 5 or 20 ng/h significantly decreased P2Y2-R protein abundance (approximately 40% of saline-treated group). In parallel, the relative expression of P2Y2-R vs. AQP2- or V2-R mRNA was significantly decreased. Furthermore, the P2Y2-R-mediated PGE(2) release by IMCD was significantly decreased in rats infused 20 ng/h but not 5 ng/h of dDAVP. Urinary PGE(2) metabolite excretion, however, did not change with dDAVP infusion. In conclusion, chronic dDAVP infusion decreases the expression and activity of P2Y2-R in IM. This may be due to a direct effect of dDAVP or dDAVP-induced increase in medullary tonicity.
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PMID:Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD. 1591 77

Aquaporins are channels that facilitate movement of water across lipid bilayers. They are expressed in multiple tissues and are essential for regulation of body water homeostasis. The kidney is the main organ responsible for this regulation, and at least seven aquaporins are expressed at distinct sites in the kidney. Aquaporin expression correlates with observed water permeability of each nephron segment: proximal tubule and descending thin limb of Henle have constitutive high water permeability due to expression of AQP1, whereas collecting duct water permeability is tightly regulated by the antidiuretic hormone vasopressin via regulation of AQP2. This review aims at providing insight into renal aquaporins, with special focus on AQP2.
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PMID:The renal plumbing system: aquaporin water channels. 1592 68

The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.
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PMID:Molecular biology of hereditary diabetes insipidus. 1609 48

Congenital nephrogenic diabetes insipidus (NDI) is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin. Human kindreds with nephrogenic diabetes insipidus have been found to harbor mutations in the vasopressin receptor 2 (Avpr2) gene or the vasopressin-sensitive water channel aquaporin-2 (Aqp2) gene. Development of a treatment is rendered difficult due to the lack of a viable animal model. Through forward genetic screening of ethylnitrosourea-mutagenized mice, we report the identification and characterization of a mouse model of NDI, with an F204V mutation in the Aqp2 gene. Unlike previously attempted murine models of NDI, our mice survive to adulthood and more exactly recapitulate the human disorder. Previous in vitro experiments using renal cell lines suggest recessive Aqp2 mutations result in improper trafficking of the mutant water pore. Using these animals, we have directly proven this hypothesis of improper AQP2 translocation as the molecular defect in nephrogenic diabetes insipidus in the intact organism. Additionally, using a renal cell line we show that the mutated protein, AQP2-F204V, is retained in the endoplasmic reticulum and that this abnormal localization can be rescued by wild-type protein. This novel mouse model allows for further mechanistic studies as well as testing of pharmacological and gene therapies for NDI.
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PMID:Diabetes insipidus in mice with a mutation in aquaporin-2. 1612 Dec 55


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