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)

The effect of vasopressin on subcellular localization of AQP-CD and AQP3 water channels was examined in thirsted Brattleboro rats by immunohistochemistry and immunoelectron microscopy. AQP-CD was mainly present in the cytoplasm of the collecting duct cells in association with cytoplasmic vesicles but was sparse in the apical membrane in control vehicle-injected rats. In rats given vasopressin 15 min before death, the number of immunogold particles for AQP-CD in the apical membrane increased significantly (P < 0.002) from 1.8 +/- 0.2 to 10.0 +/- 0.4/microns with a significant decrease (P < 0.05) of cytoplasmic labeling from 32.6 +/- 6.4 to 24.6 +/- 5.6/microns 2, indicating that AQP-CD is the vasopressin-regulated water channel predicted by the "shuttle" hypothesis. In contrast, AQP3 was restricted to the basolateral membrane of the collecting duct cells, and the labeling density of AQP3 was unchanged by vasopressin treatment, indicating that AQP3 is constitutively expressed and may maintain high water permeability of the basolateral membrane.
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PMID:Vasopressin increases AQP-CD water channel in apical membrane of collecting duct cells in Brattleboro rats. 754 41

The longstanding puzzle of membrane water permeability was advanced by the discovery of channel-forming integral protein (CHIP). This protein was shown to function as a water channel when expressed in Xenopus oocytes or when reconstituted into synthetic membranes. Site-directed mutagenesis and electron crystallography reveal tetrameric organization of CHIP, and the two halves of CHIP are tandem repeats folded into an obversely symmetric structure which resembles an hourglass. Each tetramer is comprised of functionally independent subunits. CHIP is the archetypal member of a newly-recognized family of membrane water transporters known as the "Aquaporins" (AQPs). AQP1 (CHIP) is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in a number of extra renal tissues. In the collecting duct, AQP2 is the predominant vasopressin-sensitive water channel. AQP2 is localized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by antidiuretic hormone. Humans are identified with mutations in AQP1 and AQP2 and exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of collecting duct principal cells providing an exit pathway for water, and AQP4 is abundant in brain, where it apparently functions as the hypothalamic osmoreceptor responsible for secretion of antidiuretic hormone. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and water balance disorders.
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PMID:The aquaporin family of water channels in kidney. 856 67

Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that function as molecular water channels. At least four aquaporins are expressed in the kidney where they mediate rapid water transport across water-permeable epithelia and play critical roles in urinary concentrating and diluting processes. AQP1 is constitutively expressed at extremely high levels in the proximal tubule and descending limb of Henle's loop. AQP2, -3 and -4 are expressed predominantly in the collecting duct system. AQP2 is the predominant water channel in the apical plasma membrane and AQP3 and -4 are found in the basolateral plasma membrane. Short-term regulation of collecting duct water permeability by vasopressin is largely a consequence of regulated trafficking of AQP2-containing vesicles to and from the apical plasma membrane.
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PMID:Renal aquaporins. 874 83

The longstanding puzzle of membrane water-permeability was advanced by discovery of a new class of proteins known as the "aquaporins" (AQPs). First identified in red blood cells, AQP1 was shown to function as a water channel when expressed in Xenopus oocytes or when pure AQP1 protein was reconstituted into synthetic membranes. Analysis of the primary sequence revealed that the two halves of the AQP1 polypeptide are tandem repeats; site directed mutagenesis studies indicate that the repeats may fold into an obversely symmetric structure which resembles an hourglass. Electron crystallography elucidated the tetrameric organization of AQP1, and functional studies suggest that each tetramer contains multiple functionally independent aqueous pores. AQP1 is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in multiple extra renal tissues. AQP2 is expressed only in the principal cells of renal collecting duct where it is the predominant vasopressin (ADH, antidiuretic hormone) regulated water channel. AQP2 is localized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by ADH. Humans with mutations in genes encoding AQP1 and AQP2 exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of renal collecting duct principal cells providing an exit pathway for water; AQP4 is abundant in brain where it may function as the hypothalamic osmoreceptor responsible for secretion of ADH. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and disorders of water balance.
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PMID:The aquaporin family of water channels in kidney. 898 45

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

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

In the renal collecting duct, vasopressin acutely activates cAMP production, resulting in trafficking of aquaporin-2 water channels (AQP2) to the apical plasma membrane, thereby increasing water permeability. This acute response is modulated by long-term changes in AQP2 expression. Recently, a cAMP-responsive element has been identified in the AQP2 gene, raising the possibility that changes in cAMP levels may control AQP2 expression. To investigate this possibility, we determined AQP2 protein levels in a strain of mice, DI +/+ severe (DI), which have genetically high levels of cAMP-phosphodiesterase activity, and hence low cellular cAMP levels, and severe polyuria. Semiquantitative immunoblotting of membrane fractions prepared from whole kidneys revealed that AQP2 levels in DI mice were only 26 +/- 7% (+/-SE) of those in control mice (n = 10, P < 0.01). In addition, semiquantitative Northern blotting revealed a significantly lower AQP2 mRNA expression in kidneys from DI mice compared with control mice (43 +/- 6% vs. 100 +/- 10%; n = 6 in each group, P < 0.05). AQP3 levels were also reduced. The mice were polyuric and urine osmolalities were accordingly substantially lower in the DI mice than in controls (496 +/- 53 vs. 1,696 +/- 105 mosmol/kgH2O, respectively). Moreover, there was a linear correlation between urine osmolalities and AQP2 levels (P < 0.05). Immunoelectron microscopy confirmed the markedly lower expression of AQP2 in collecting duct principal cells in kidneys of DI mice and, furthermore, demonstrated that AQP2 was almost completely absent from the apical plasma membrane. Thus expression of AQP2 and AQP2 trafficking were severely impaired in DI mice. These results are consistent with the view that in vivo regulation of AQP2 expression by vasopressin is mediated by cAMP.
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PMID:Low aquaporin-2 levels in polyuric DI +/+ severe mice with constitutively high cAMP-phosphodiesterase activity. 995 Sep 48

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

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


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