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

In congenital nephrogenic diabetes insipidus, the renal collecting ducts are resistant to the antidiuretic action of arginine vasopressin or to its antidiuretic analog 1-deamino[8-D-arginine] vasopressin (dDAVP). This is a rare, but now well described entity secondary to either mutations in the AVPR2 gene that codes for the vasopressin antidiuretic (V2) receptor or to mutations in the AQP2 gene that codes for the vasopressin-dependent water channel. A majority (> 90%) of congenital nephrogenic diabetes insipidus patients have AVPR2 mutations: Of 115 families with congenital nephrogenic diabetes insipidus, 105 families had AVPR2 mutations, and 10 had AQP2 mutations. When studied in vitro, most AVPR2 mutations lead to receptors that are trapped intracellularly and are unable to reach the plasma membrane. A minority of the mutant receptors reach the cell surface but are unable to bind vasopressin or to trigger an intracellular adenosine 3:5-cyclic phosphate signal properly. Most of the reported mutations are secondary to a complete loss of function of the receptor, and only a few mutations have been associated with a mild phenotype. These advances provide diagnostic tools for physicians caring for these patients because, when the disease causing mutation has been identified, carrier and perinatal testing could be done by mutation analysis.
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PMID:Vasopressin receptor mutations causing nephrogenic diabetes insipidus. 975 88

In the past year, significant progress has been achieved in the research on aquaporins (AQPs), a family of structurally related molecular water channels. Three novel AQPs were identified, giving a total of ten mammalian AQPs. An important step forward in identifying the aqueous pore in AQP molecules was the determination of the three-dimensional structure of AQP1. The expression pattern of individual AQPs in different tissues was determined in more detail and AQP-knockout mice have been generated. The discovery of a severe urinary concentrating defect in AQP1-knockout mice was remarkable. Only AQP2, the vasopressin-sensitive water channel in the kidney, which is mutated in autosomal recessive and dominant cases of nephrogenic diabetes insipidus, has been shown to be involved in human disease. The finding of changed AQP2 expression in several acquired water balance disorders may pave the way toward developing treatments for these clinical problems.
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PMID:Aquaporin molecular biology and clinical abnormalities of the water transport channels. 975 70

Urinary concentration characteristically decreases in response to a reduction in renal mass in chronic renal failure (CRF). In the present study, we examined whether there are changes in the expression of aquaporins in rats where CRF was induced by 5/6 nephrectomy. Plasma creatinine levels were significantly elevated consistent with significant CRF: 135.7 +/- 15.1 (n = 17, CRF) vs. 33. 9 +/- 1.1 micromol/l (n = 11, sham), P < 0.05. Two weeks after 5/6 nephrectomy, the remnant kidneys were hypertrophied, and total renal mass increased to 65 +/- 3% of sham levels (P < 0.05). Urine production increased markedly from 40 +/- 2 to 111 +/- 3 microliter. min-1. kg-1 in CRF rats (P < 0.05), whereas urine osmolality and solute-free water reabsorption decreased significantly. Quantitative immunoblotting of total kidney membrane fractions revealed a significant decrease in total kidney AQP2 expression in CRF rats to 43 +/- 12% of sham levels (P < 0.05). A similar reduction was observed for AQP1 and AQP3. Furthermore, the increased urine output and decreased urine osmolality persisted in CRF rats despite 7 days treatment with 1-desamino-[8-D-arginine]vasopressin (DDAVP, 0.1 microgram/h sc) compared with untreated sham-operated controls. Also, there was no change in AQP2 expression (which remained at 38 +/- 3% of sham levels, P < 0.05), urine output, or urine osmolality between CRF rats with or without DDAVP treatment. Immunocytochemistry confirmed the decreased AQP2 expression in collecting duct principal cells in CRF rats, with a predominant apical labeling. In conclusion, the results demonstrated that there was a significant vasopressin-resistant downregulation of AQP2 and AQP3 as well as downregulation of AQP1 associated with the polyuria in CRF rats.
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PMID:Reduced AQP1, -2, and -3 levels in kidneys of rats with CRF induced by surgical reduction in renal mass. 981 30

Several aquaporin-type water channels are expressed in mammalian kidney and lung: AQP1 in lung microvessels and kidney proximal tubule, thin descending limb of Henle, and vasa recta; AQP2 in apical membrane of collecting duct epithelium; AQP3 and AQP4 in basolateral membranes of airway and collecting duct epithelium; and AQP5 in alveolar epithelium. Novel quantitative fluorescence methods demonstrated very high water permeabilities of the alveolar epithelial and endothelial barriers, and moderately high water permeability across distal airways. In the kidney, water permeability is high in proximal tubule and thin descending limb of Henle, and regulated by vasopressin in collecting duct. The author's laboratory has studied the role of aquaporins in organ physiology using transgenic knockout mice lacking specific aquaporins. AQP1 null mice are mildly growth-retarded, manifest a severe urinary concentrating defect, and have reduced water permeability between airspace and capillary compartments. AQP4 null mice appear normal grossly except for a mild defect in maximum urinary concentrating ability. AQP2-deficient humans have hereditary non-X-linked nephrogenic diabetes insipidus (NDI). In transfected mammalian cells, many NDI-causing AQP2 mutants are retained in the endoplasmic reticulum. The author's laboratory has found that "chemical chaperones," that is, small compounds that promote protein folding in vitro, are able to correct defective AQP2 trafficking in cell culture models. The transgenic mouse and mammalian cell models are thus beginning to provide clues about the role of aquaporins in normal physiology and disease.
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PMID:Role of aquaporin water channels in kidney and lung. 982 13

The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.
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PMID:Physiology and pathophysiology of renal aquaporins. 1007 16

OBJECTIVE: To develop radioimmunoassay for aquaporin-2 (AQP-2). METHODS: Anti-AQP-2 antiserum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic AQP-2 peptide (257-271) with bovine serum albumin. Radioiodination of synthetic peptide (tyrosine-AQP2 (257-271) was performed by chloramine T method, followed by purification of radioiodinated material on Sephadex G-25 column. RESULTS: The obtained antibody did not crossreact with vasopressin, pituitary hormones, hypothalamic hormones and neuropeptides. The assay was performed with a double antibody system. The values are expressed as an equivalent of synthetic AQP-2 peptide (257-271). The dilution curve of high AQP-2 urine in radioimmunoassay system was parallel to the standard curve. The recovery percentage of AQP-2 added to urine was about 100 % in this assay system. Intra-assay and inter-assay variation was 4.5 % and 7.2 %, respectively. Mean urinary excretion of AQP-2 was 1.16 ng equivalent of AQP-2 (257-271)/mg creatine and was lower in patients with diabetes insipidus. CONCLUSION: These data suggest that his assay system is a suitable to measure AQP-2 in urine.
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PMID:Radioimmunoassay for Aquaporin-2. 1019 11

Several aquaporin-type water channels are expressed in kidney: AQP1 in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2, AQP3, and AQP4 in the collecting duct; AQP6 in the papilla; and AQP7 in the proximal tubule. AQP2 is the vasopressin-regulated water channel that is important in hereditary and acquired diseases affecting urine-concentrating ability. It has been difficult to establish the roles of the other aquaporins in renal physiology because suitable aquaporin inhibitors are not available. One approach to the problem has been to generate and analyze transgenic knockout mice in which individual aquaporins have been selectively deleted by targeted gene disruption. Phenotype analysis of kidney and extrarenal function in knockout mice has been very informative in defining the role of aquaporins in organ physiology and addressing basic questions regarding the route of transepithelial water transport and the mechanism of near iso-osmolar fluid reabsorption. This article describes new renal physiologic insights revealed by phenotype analysis of aquaporin-knockout mice and the prospects for further basic and clinical developments.
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PMID:Lessons on renal physiology from transgenic mice lacking aquaporin water channels. 1023

The early 90s have brought us a discovery of a new class of membrane proteins--aquaporins with a function of transmembrane water channels. Being genetically closed proteins aquaporins are members of a large family of channel-forming proteins called MIPs (major intrinsic proteins). All aquaporins, except AQP4, are mercury-sensitive. Many aquaporins have been cloned and identified. Polyclonal antibodies grown against some of them promoted numerous studies of aquaporin localization and distribution in animal and plant tissues. Up to the present, 10 and 2 aquaporins have been described in mammalian and amphibian epithelial tissues, respectively. One of described aquaporins, AQP2, whose localization is confined to kidney collecting duct principal cells, has been found to be a hormone-depending water channel. The insertion of apical vesicles bearing AQP2 was shown to be regulated by vasopressin, meanwhile all other aquaporins are inserted into the plasma membrane constitutively. There is a vast evidence showing that the integrity of microtubules is necessary for both pathways of aquaporin insertion. AQP2 is important for normal kidney functioning and AQP2 mutations cause water-balance disorders. On the contrary, the AQP1 mutations are not accompanied by any evident clinical pathology. This review is focused on a discussion of the data so far available on aquaporin distribution in different animal tissues.
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PMID:[Aquaporins of plasma membranes of epithelial cells]. 1059 Nov 24

Phosphorylation of Ser(256), in a PKA consensus site, in AQP2 (p-AQP2) appears to be critically involved in the vasopressin-induced trafficking of AQP2. In the present study, affinity-purified antibodies that selectively recognize AQP2 phosphorylated at Ser(256) were developed. These antibodies were used to determine 1) the subcellular localization of p-AQP2 in rat kidney and 2) changes in distribution and/or levels of p-AQP2 in response to [desamino-Cys(1),D-Arg(8)]vasopressin (DDAVP) treatment or V(2)-receptor blockade. Immunoelectron microscopy revealed that p-AQP2 was localized in both the apical plasma membrane and in intracellular vesicles of collecting duct principal cells. Treatment of rats with V(2)-receptor antagonist for 30 min resulted in almost complete disappearance of p-AQP2 labeling of the apical plasma membrane with only marginal labeling of intracellular vesicles remaining. Immunoblotting confirmed a marked decrease in p-AQP2 levels. In control Brattleboro rats (BB), lacking vasopressin secretion, p-AQP2 labeling was almost exclusively present in intracellular vesicles. Treatment of BB rats with DDAVP for 2 h induced a 10-fold increase in p-AQP2 labeling of the apical plasma membrane. The overall abundance of p-AQP2, however, was not increased, as determined both by immunoelectron microscopy and immunoblotting. Consistent with this, 2 h of DDAVP treatment of normal rats also resulted in unchanged p-AQP2 levels. Thus the results demonstrate that AQP2 phosphorylated in Ser(256) is present in the apical plasma membrane and in intracellular vesicles and that both the intracellular distribution/trafficking, as well as the abundance of p-AQP2, are regulated via V(2) receptors by altering phosphorylation and/or dephosphorylation of Ser(256) in AQP2.
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PMID:Localization and regulation of PKA-phosphorylated AQP2 in response to V(2)-receptor agonist/antagonist treatment. 1064 53

Aquaporins are transmembrane proteins mediating water transport across plasma membrane of animal, vegetal or bacterial cells. Among the ten aquaporins known in mammals, six are located in kidney and take part in urine concentration. AQP2 is vasopressin regulated, it is the only family member to be implicated in human pathology, such as nephrogenic diabetes insipidus, congestive heart failure, hepatic cirrhosis, nephrotic syndrome or SIADH. Aquaporins are expressed in a wide variety of tissues, such as brain or gastrointestinal tractus, and suggest a role in water tissue exchange, but their real function is still not define. To know the physiological impact of aquaporins, AQP1, AQP3, AQP4 and AQP5 knockout mice have been created and their phenotype analysed.
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PMID:[New players in the physiopathology of water metabolism: the aquaporins]. 1066 46


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