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 aquaporin water channels are expressed in various fluid-transporting epithelia. Physiological and genetic investigations have revealed that aquaporin channel-like intrinsic protein is expressed in numerous tissues, but its significance in water transport physiology is unclear. It has been shown that aquaporin-collecting duct is a vasopressin-responsive water channel, and that it is regulated by a membrane shuttle mechanism. Three unique models for a water pore have been presented but further studies will be required to verify them. New aquaporin members have been isolated and their discrete localization may reflect their specific physiological roles.
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PMID:Water channels. 856 40

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

The aquaporins are a family of transmembrane proteins that function as molecular water channels. Recently, a mercurial-insensitive water channel [MIWC or aquaporin-4 (AQP4)] has been cloned, and its mRNA was found to be expressed strongly in kidney inner medulla and several nonrenal tissues. We prepared affinity-purified polyclonal antipeptide antibodies to AQP4 to define the regional distribution and cellular location of this water channel within the kidney. Immunoblotting of membrane fractions from different regions of the kidney revealed strongest expression in the base of the renal inner medulla, with detectable levels also in the inner medullary tip, but little or no expression in the outer medulla or cortex. Immunocytochemistry (light microscopy) revealed renal AQP4 labeling exclusively in the collecting duct principal cells, chiefly in the proximal two-thirds of the inner medullary collecting duct (IMCD). Little or no expression was seen in the outer medullary and cortical collecting ducts. Immunoelectron microscopy demonstrated AQP4 labeling of the basolateral membrane of IMCD cells, with relatively little labeling of intracellular vesicles. Differential centrifugation of inner medullary homogenates also revealed a lack of distribution to the vesicle-enriched fraction, which contains the vasopressin-regulated water channel, aquaporin-2. In contrast to aquaporin-2 and aquaporin-3, water restriction of rats did not increase the level of AQP4 expression. These results suggest a possible role for AQP4 in the basolateral exit of water from the IMCD.
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PMID:Distribution of aquaporin-4 water channel expression within rat kidney. 859 71

We determined whether aquaporin of collecting duct (AQP-CD) is involved in pathogenesis of water retention in rats with experimental models of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and liver cirrhosis. SIADH rats were made by administering 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously and providing them with a liquid diet. Serum Na levels decreased to < 120 meq/l on day 2, and hyponatremia persisted throughout the rest of observation period. Six hours after the DDAVP infusion, the expression of AQP-CD mRNA significantly increased by 198%, followed by > 144% increases in its expression during the 14-day observation period. On day 7, the increased expression of AQP-CD mRNA was abolished after the administration of an antidiuretic, nonpeptide arginine vasopressin (AVP) antagonist, OPC-31260, which was closely related to a marked diuresis and a prompt normalization of serum Na levels in SIADH rats. Rats were made cirrhotic by injecting a mixture of carbon tetrachloride and olive oil subcutaneously for 3 mo. The expression of AQP-CD mRNA was increased by 164% in the decompensated cirrhotic rats. The blockade of AVP action by OPC-31260 significantly diminished its expression. These results indicate that water channel AQP-CD plays an important role in water retention in pathological states of SIADH and liver cirrhosis.
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PMID:Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats. 859 89

Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel in the kidney collecting duct. AQP-2 is selectively permeable to water molecule and is translocated between the apical membrane and subapical endosomes in response to vasopressin. To investigate the localization and structure of the aqueous pathway of the AQP-2 water channel, a series of site-directed mutants was constructed and functionally analyzed. Insertion of N-glycosylation reporter sequence into each hydrophilic loop (HL) indicated that AQP-2 has a six-membrane spanning topology and that insertional mutations in HL-2 or HL-5 do not alter water channel function. Mercury-sensitive site of AQP-2 is located near the second asparagine-proline-alanine (NPA) domain at cysteine 181, but not near the first NPA domain. Replacement of HL-3 or HL-4 with the corresponding part of Escherichia coli glycerol facilitator abolished water channel function without changing plasma membrane expression of the channel protein. Introduction of cysteine residues in His-122, Asn-123, Gly-154, Asp-155, or Asn-156 induced partial mercury sensitivity, and point mutations in asparagine 123 significantly altered water permeability. Our results implicate that the structure of AQP-2 is different from models previously proposed for AQP-1 and that HL-3 and HL-4 are closely located to the aqueous pathway.
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PMID:Structure of aquaporin-2 vasopressin water channel. 861 98

Prolonged hypokalemia causes vasopressin-resistant polyuria. We have recently shown that another cause of severe polyuria, chronic lithium therapy, is associated with decreased aquaporin-2 (AQP2) water channel expression (Marples, D., S. Christensen, E.I. Christensen, P.D. Ottosen, and S. Nielsen, 1995. J. Clin. Invest., 95: 1838-1845). Consequently, we studied the effect in rats of 11 days' potassium deprivation on urine production and AQP2 expression and distribution. Membrane fractions were prepared from one kidney, while the contralateral kidney was perfusion-fixed for immunocytochemistry. Immunoblotting and densitometry revealed a decrease in AQP2 levels to 27+/-3.4% of control levels (n=11, P<0.001) in inner medulla, and 34+/-15% of controls (n=5, P<0.05) in cortex. Urine production increased in parallel, from 11+/-1.4 to 30+/-4.4 ml/day (n=11, P<0.01). After return to a potassium-containing diet both urine output and AQP2 labels normalized within 7 d. Immunocytochemistry confirmed decreased AQP2 labeling in principal cells of both inner medullary and cortical collecting ducts. AQP2 labeling was predominantly associated with the apical plasma membrane and intracellular vesicles. Lithium treatment for 24 d caused a more extensive reduction of AQP2 levels, to 4+/-1% of control levels in the inner medulla and 4+/-2% in cortex, in association with severe polyuria. The similar degree of downregulation in medulla and cortex suggests that interstitial tonicity is not the major factor in the regulation of AQP2 expression. Consistent with this furosemide treatment did not alter AQP2 levels. In summary,hypokalemia, like lithium treatment, results in a decrease in AQP2 expression in rat collecting ducts, in parallel with the development of polyuria, and the degree of downregulation is consistent with the level of polyuria induced, supporting the view that there is a causative link.
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PMID:Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex. 862 81

The renal urea transporter (RUT) is responsible for urea accumulation in the renal medulla, and consequently plays a central role in the urinary concentrating mechanism. To study its cellular and subcellular localization, we prepared affinity-purified, peptide-derived polyclonal antibodies against rat RUT based on the cloned cDNA sequence. Immunoblots using membrane fractions from rat renal inner medulla revealed a solitary 97-kDa band. Immunocytochemistry demonstrated RUT labeling of the apical and subapical regions of inner medullary collecting duct (IMCD) cells, with no labeling of outer medullary or cortical collecting ducts. Immunoelectron microscopy directly demonstrated labeling of the apical plasma membrane and of subapical intracellular vesicles of IMCD cells, but no labeling of the basolateral plasma membrane. Immunoblots demonstrated RUT labeling in both plasma membrane and intracellular vesicle-enriched membrane fractions from inner medulla, a subcellular distribution similar to that of the vasopressin-regulated water channel, aquaporin-2. In the outer medulla, RUT labeling was seen in terminal portions of short-loop descending thin limbs. Aside from IMCD and descending thin limbs, no other structures were labeled in the kidney. These results suggest that: (i) the RUT provides the apical pathway for rapid, vasopressin-regulated urea transport in the IMCD, (ii) collecting duct urea transport may be increased by vasopressin by stimulation of trafficking of RUT-containing vesicles to the apical plasma membrane, and (iii) the rat urea transporter may provide a pathway for urea entry into the descending limbs of short-loop nephrons.
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PMID:Cellular and subcellular localization of the vasopressin- regulated urea transporter in rat kidney. 864 3

The arcades are long, branched renal tubules which connect deep and mid-cortical nephrons to cortical collecting ducts in the renal cortex. Because they are inaccessible by standard physiological techniques, their functions are poorly understood. In this paper, we demonstrate that the arcades are a site of expression of two proteins, aquaporin-2 (the vasopressin-regulated water channel) and the V2 vasopressin receptor, that are important to regulated water transport in the kidney. Using a peptide-derived polyclonal antibody to aquaporin-2, quantitative ELISA in microdissected segments showed that aquaporin-2 is highly expressed in arcades and that the expression is increased in response to restriction of fluid intake. Immunocytochemistry revealed abundant aquaporin-2 labeling of structures in the cortical labyrinth in a pattern similar to that of the Na(+)-Ca2+ exchanger and kallikrein, marker proteins expressed in arcades but not in cortical collecting ducts. RT-PCR experiments demonstrated substantial aquaporin-2 and V2 receptor mRNA in microdissected arcades. In situ hybridization, using 35S-labeled antisense cRNA probes for the V2 receptor demonstrated strong labeling of both arcades and cortical collecting ducts. Thus, these results indicate that the arcades contain the specific proteins associated with vasopressin-regulated water transport, and may be a heretofore unrecognized site of free water absorption.
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PMID:Rat renal arcade segment expresses vasopressin-regulated water channel and vasopressin V2 receptor. 867 87

1. The effect of the dynein inhibitor erythro-9-[3-(2-hydroxynonyl)] adenine (EHNA) on the osmotic water flow response to vasopressin or exogenous cAMP has been investigated in isolated toad urinary bladders. 2. Pretreatment with serosal EHNA had no effect on basal water flow, but inhibited the development and maintenance of the hydrosmotic response to vasopressin (20 mU ml-1) or 8-(4-parachlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8 CPT-cAMP; 0.1 mM). 3. The inhibitory effect of EHNA on vasopressin-induced water flow was dose dependent. Inhibition occurred in the dose range in which EHNA inhibits the ATPase and motor activities of dynein in vitro. 4. EHNA also inhibited the maintenance of the high rate of water flow established by prior exposure to vasopressin. 5. The inhibitory effect of EHNA on the onset phase of the vasopressin response was attenuated after exposure of the tissue to the microtubule-disruptive drug nocodazole but was fully additive with that of cytochalasin B. 6. EHNA inhibited basal and vasopressin-stimulated transepithelial sodium transport. 7. The findings support the view that EHNA inhibits hormone-induced water flow through an action on a cytoplasmic dynein. The results are consistent with the hypothesis that dynein is involved in the microtubule-based delivery of water channel-containing vesicles to the apical membrane of the granular epithelial cells during both the onset and maintenance of the water permeability response to vasopressin.
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PMID:Effect of a dynein inhibitor on vasopressin action in toad urinary bladder. 868 74

Hereditary diabetes insipidus can occur in two forms: the first, referred to as central diabetes insipidus, is responsive to vasopressin whereas the second, termed nephrogenic diabetes insipidus, is resistant to treatment. Recent advances in molecular genetics have contributed to elucidate the pathogenesis of these affections. Familial central diabetes insipidus depicts two unsimilar illnesses. The first, characterized by an autosomal dominant transmission, is of delayed onset and worsens progressively all through life. It is related to a heterozygous mutation of the vasopressin precursor gene mainly involving either the sequence encoding for the signal peptide or the one encoding for neurophysin II, the hormone carrier protein. Mutations described to date are responsible for impairment of vasopressin precursor transportation and processing. Therefore mutant protein accumulates in the posterior pituitary which is involved in the persistant bright spot seen on magnetic resonance imaging. The second illness or Wolfram syndrome, autosomal recessive, associates obligatory features: insulin-dependant diabetes, bilateral optic atrophy and more inconstantly: diabetes insipidus, deafness, genito-urinary and neuropsychiatric disturbances. The cause of this syndrome, still unknown, may involve mitochondrial ADN mutations. Familial nephrogenic diabetes insipidus, of neonatal onset, are mainly X-linked and associated to mutations in the V2 receptor gene. About 60 mutations have been described until now. Some rare cases, transmission of which is autosomal recessive, result from homozygous mutations of aquaporin 2 gene, a water channel involved in the water reabsorption in the renal collecting duct. Other mutations will be probably discovered in future. In conclusion, familial diabetes insipidus constitutes an interesting pathogenic model because it may be explained by impairment of vasopressin gene precursor as well as by abnormalities of renal receptor or post receptor mechanisms of the hormone.
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PMID:[Congenital diabetes insipidus. Recent advances in molecular genetics]. 868 70


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