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 aquaporins (AQP) are a family of small transmembrane water channels. The discovery of AQP has provided insight into molecular mechanisms underlying renal water absorption and its regulation by vasopressin. Seven types of AQP have been identified in the kidney. AQP1 has been localized in the proximal tubule and descending thin limb, while AQP2, AQP3, and AQP4 are expressed in the collecting duct. Of these isoforms, AQP2 expression and intracellular trafficking is tightly regulated by vasopressin. Decreased expression of renal AQP has been detected in several disorders associated with polyuria and impaired ability to concentrate urine, as exemplified by nephrogenic diabetes insipidus or renal failure. In contrast, increased expression of AQP is seen in conditions leading to water retention, such as congestive heart failure, liver cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion. Thus, the understanding of molecular structure and function of aquaporins may have important implications for therapy of water balance disorders.
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PMID:[Aquaporin water channels in water balance regulation in the kidney]. 1273 79

Arginine-vasopressin (AVP) facilitates water reabsorption in renal collecting duct principal cells by activation of vasopressin V2 receptors and the subsequent translocation of water channels (aquaporin-2, AQP2) from intracellular vesicles into the plasma membrane. Prostaglandin E2 (PGE2) antagonizes AVP-induced water reabsorption; the signaling pathway underlying the diuretic response is not known. Using primary rat inner medullary collecting duct (IMCD) cells, we show that stimulation of prostaglandin EP3 receptors induced Rho activation and actin polymerization in resting IMCD cells, but did not modify the intracellular localization of AQP2. However, AVP-, dibutyryl cAMP- and forskolin-induced AQP2 translocation was strongly inhibited. This inhibitory effect was independent of increases in cAMP and cytosolic Ca2+. In addition, stimulation of EP3 receptors inhibited the AVP-induced Rho inactivation and the AVP-induced F-actin depolymerization. The data suggest that the signaling pathway underlying the diuretic effects of PGE2 and probably those of other diuretic agents include cAMP- and Ca2+-independent Rho activation and F-actin formation.
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PMID:The prostaglandin E2 analogue sulprostone antagonizes vasopressin-induced antidiuresis through activation of Rho. 1282 46

The apical Na+-H+ exchanger NHE3 plays an important role in fluid reabsorption in the proximal tubule. However, whether its deletion alters the salt and water transport in the distal nephron remains unknown. To answer these questions, wild-type (Nhe3+/+) and NHE3 null mice (Nhe3-/-) were placed in metabolic cages and their water balance and urine osmolality were examined. Nhe3-/- mice demonstrated a significant polydipsia (P < 0.03) and polyuria (P < 0.04), with a lower urine osmolality (P < 0.003) as compared to Nhe3+/+ mice. Northern hybridization and immunoblotting studies indicated that the mRNA expression and protein abundance of the collecting duct (CD) water channel AQP2 decreased by 52 % (P < 0.0003) and 73 % (P < 0.003) in the cortex, and by 53 % and 54 % (P < 0.002) in the inner medulla (IM) of Nhe3-/- vs. Nhe3+/+ mice. The expression of AQP2 in the outer medulla (OM) remained unchanged. Further, the mRNA expression and protein abundance of the medullary thick ascending limb (mTAL) apical Na+-K+-2Cl- cotransporter (NKCC2) decreased by 52 % (P < 0.02) and 44 % (P < 0.01), respectively, in the OM of Nhe3-/- vs. Nhe3+/+ mice. The circulating plasma levels of vasopressin as well as the mRNA expression of vasopressin prohormone were significantly increased in Nhe3-/- vs. Nhe3+/+ mice (P < 0.05). Studies in mice treated with acetazolamide indicated that increased bicarbonate and fluid delivery to distal nephron did not alter the expression of NKCC2 in mTAL and decreased AQP2 protein only in OM but not in the cortex or IM. In conclusion, mice lacking the apical NHE3 have impairment in their water balance and urine osmolality, which correlates with the downregulation of AQP2 expression. These defects occur despite increased circulating levels of vasopressin. We propose that an ADH-independent mechanism is responsible for the downregulation of AQP2 and the resulting polyuria in NHE3 null mice.
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PMID:Downregulation of renal AQP2 water channel and NKCC2 in mice lacking the apical Na+-H+ exchanger NHE3. 1450 Jul 65

In mammals, the regulation of water homeostasis is mediated by the aquaporin-1 (AQP1) water channel, which localizes to the basolateral and apical membranes of the early nephron segment, and AQP2, which is translocated from intracellular vesicles to the apical membrane of collecting duct cells after vasopressin stimulation. Because a similar localization and regulation are observed in transfected Madin-Darby Canine Kidney (MDCK) cells, we investigated which segments of AQP2 are important for its routing to forskolin-sensitive vesicles and the apical membrane through analysis of AQP1-AQP2 chimeras. AQP1 with the entire COOH tail of AQP2 was constitutively localized in the apical membrane, whereas chimeras with shorter COOH tail segments of AQP2 were localized in the apical and basolateral membrane. AQP1 with the NH2 tail of AQP2 was constitutively localized in both plasma membranes, whereas AQP1 with the NH2 and COOH tail of AQP2 was sorted to intracellular vesicles and translocated to the apical membrane with forskolin. These data indicate that region N220-S229 is essential for localization of AQP2 in the apical membrane and that the NH2 and COOH tail of AQP2 are essential for trafficking of AQP2 to intracellular vesicles and its shuttling to and from the apical membrane.
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PMID:Role of cytoplasmic termini in sorting and shuttling of the aquaporin-2 water channel. 1456 91

The aim of this study was to evaluate the long-term effects of cyclosporine (CsA) treatment on urinary concentration ability. Rats were treated daily for 4 wk with vehicle (VH; olive oil, 1 ml/kg sc) or CsA (15 mg/kg sc). The influence of CsA on the kidney's ability to concentrate urine was evaluated using functional parameters and expression of aquaporins (AQP1-4) and of urea transporters (UT-A-1-3, and UT-B). Plasma vasopressin levels and the associated signal pathway were evaluated, and the effect of vasopressin infusion on urine concentration was observed in VH- and CsA-treated rats. Toxic effects of CsA on tubular cells in the medulla as well as the cortex were evaluated with aldose reductase (AR), Na-K-ATPase-alpha(1) expression, and by determining the number of terminal transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Long-term CsA treatment increased urine volume and fractional excretion of sodium and decreased urine osmolality and free-water reabsorption compared with VH-treated rats. These functional changes were accompanied by decreases in the expression of AQP (1-4) and UT (UT-A2, -A3, and UT-B), although there was no change in AQP2 in the cortex and outer medulla and UT-A1 in the inner medulla (IM). Plasma vasopressin levels were not significantly different between two groups, but infusion of vasopressin restored CsA-induced impairment of urine concentration. cAMP levels and Gsalpha protein expression were significantly reduced in CsA-treated rat kidneys compared with VH-treated rat kidneys. CsA treatment decreased the expression of AR and Na-K-ATPase-alpha(1) and increased the number of TUNEL-positive renal tubular cells in both the cortex and medulla. Moreover, the number of TUNEL-positive cells correlated with AQP2 or UT-A3) expression within the IM. In conclusion, CsA treatment impairs urine-concentrating ability by decreasing AQP and UT expression. Apoptotic cell death within the IM at least partially accounts for the CsA-induced urinary concentration defect.
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PMID:Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney. 1487 80

This study evaluates the effect of prolonged ethanol ingestion on the renal ability to concentrate urine. Suckling Wistar rats born to mothers given ethanol before and during gestation and suckling periods (ethanol-exposed offspring) were used and the results were compared with those obtained from offspring of dams given diets containing no ethanol. Comparisons were also made between progenitors with or without prolonged ethanol ingestion. Body and kidney weights; arginine-vasopressin (AVP) and aldosterone plasma levels; plasma, urine and renal papillary osmolality; urine outflow; kidney AQP2, AQP3 and AQP4 expression and diencephalon AVP mRNA expression were determined. As compared with control offspring, the ethanol-exposed offspring present i) lower body and kidney weights; ii) lower urine outflow; iii) higher renal AQP2 and AQP3 mRNA; iv) higher renal AQP2 protein content and v) higher urine and renal papillary osmolality. These changes were also observed in the ethanol-treated progenitors, although they were of smaller magnitude. Plasma osmolality, renal AQP4 mRNA, AVP plasma levels and diencephalon AVP mRNA expression were not affected by the ethanol treatment. Plasma levels of aldosterone were only significantly increased in the ethanol-exposed suckling rats. It is concluded that maternal ethanol ingestion before and during gestation and suckling periods affects the renal function of the offspring, up-regulating renal AQP2 expression by an AVP-independent mechanism. Ethanol-treated progenitors manifest similar renal changes, although of lesser magnitude than the offspring.
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PMID:Prolonged ethanol ingestion increases renal AQP2 and AQP3 expression in adult rats and in their offspring. 1513 48

Both mammals and birds can concentrate urine hyperosmotic to plasma via a countercurrent multiplier mechanism, although evolutionary lines leading to mammals and birds diverged at an early stage of tetrapod evolution. We reported earlier (Nishimura H, Koseki C, and Patel TB. Am J Physiol Regul Integr Comp Physiol 271: R1535-R1543, 1996) that arginine vasotocin (AVT; avian antidiuretic hormone) increases diffusional water permeability in the isolated, perfused medullary collecting duct (CD) of the quail kidney. In the present study, we have identified an aquaporin (AQP) 2 homolog water channel in the medullary cones of Japanese quail, Coturnix coturnix (qAQP2), by RT-PCR-based cloning techniques. A full-length cDNA contains an 822-bp open reading frame that encodes a 274-amino acid sequence with 75.5% identity to rat AQP2. The qAQP2 has six transmembrane domains, two asparagine-proline-alanine (NPA) sequences, and putative N-glycosylation (asparagine-124) and phosphorylation sites (serine-257) for cAMP-dependent protein kinase. qAQP2 is expressed in the membrane of Xenopus laevis oocytes and significantly increased its osmotic water permeability (P(f)), inhibitable (P < 0.01) by mercury chloride. qAQP2 mRNA (RT-PCR) was detected in the kidney; medullary mRNA levels were higher than cortical levels. qAQP2 protein that binds to rabbit anti-rat AQP2 antibody is present in the apical/subapical regions of both cortical and medullary CDs from normally hydrated quail, and the intensity of staining increased only in the medullary CDs after water deprivation or AVT treatment. The relative density of the approximately 29-kDa protein band detected by immunoblot from the medullary cones was modestly higher in water-deprived/AVT-treated quail. The results suggest that 1) medullary CDs of quail kidneys express a mercury-sensitive functioning qAQP2 water channel, and 2) qAQP2 is at least partly regulated by an AVT-dependent mechanism. This is the first clear identification of AQP2 homolog in nonmammalian vertebrates.
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PMID:Molecular and functional characterization of a vasotocin-sensitive aquaporin water channel in quail kidney. 1520 86

In humans, the urinary aquaporin-2 (U-AQP2) excretion closely parallels changes in vasopressin (VP) action and has been proposed as a marker for collecting duct responsiveness to VP. This report describes the development of a radioimmunoassay for the measurement of U-AQP2 excretion in dogs. In addition, the localization of AQP2 in the canine kidney was investigated by immunohistochemistry. Basal U-AQP2 excretion was highly variable among healthy dogs. Two hours after oral water loading, the mean U-AQP2/creatinine ratio decreased significantly from (231 +/- 30) x 10(-9) to (60 +/- 15) x 10(-9) (P = 0.01), while the median plasma VP concentration decreased from 4.2 pmol/l (range 2.2-4.8 pmol/l) to 1.2 pmol/l (range 1.0-1.9 pmol/l). Subsequent intravenous administration of desmopressin led to a significantly increased mean U-AQP2/creatinine ratio of (258 +/- 56) x 10(-9) (P = 0.01). Two hours of intravenous hypertonic saline infusion (20% NaCl, 0.03 ml/kg body weight/min) significantly increased the mean U-AQP2/creatinine ratio from (86 +/- 6) x 10(-9) to (145 +/- 23) x 10(-9) (P = 0.045), while the median plasma VP concentration increased significantly from 2.2 pmol/l (range 1.1-6.3 pmol/l) to 17.1 pmol/l (range 8.4-67 pmol/l) (P < 0.001). Immunohistochemistry revealed extensive labeling for AQP2 in the kidney collecting duct cells, predominantly localized in the apical and subapical region. As in humans, U-AQP2 excretion in dogs closely reflects changes in VP exposure. Urinary AQP2 excretion may become a diagnostic tool in dogs for the differentiation of polyuric conditions such as (partial) central or nephrogenic diabetes insipidus, primary polydipsia, and inappropriate VP release.
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PMID:Urinary aquaporin-2 excretion in dogs: a marker for collecting duct responsiveness to vasopressin. 1521 33

Aquaporins (AQP) are integral membrane proteins that serve as channels in the transfer of water, and in some cases, small solutes across the membrane. They are conserved in bacteria, plants, and animals. Structural analyses of the molecules have revealed the presence of a pore in the center of each aquaporin molecule. In mammalian cells, more than 10 isoforms (AQP0-AQP10) have been identified so far. They are differentially expressed in many types of cells and tissues in the body. AQP0 is abundant in the lens. AQP1 is found in the blood vessels, kidney proximal tubules, eye, and ear. AQP2 is expressed in the kidney collecting ducts, where it shuttles between the intracellular storage sites and the plasma membrane under the control of antidiuretic hormone (ADH). Mutations of AQP2 result in diabetes insipidus. AQP3 is present in the kidney collecting ducts, epidermis, urinary, respiratory, and digestive tracts. AQP3 in organs other than the kidney may be involved in the supply of water to them. AQP4 is present in the brain astrocytes, eye, ear, skeletal muscle, stomach parietal cells, and kidney collecting ducts. AQP5 is in the secretory cells such as salivary, lacrimal, and sweat glands. AQP5 is also expressed in the ear and eye. AQP6 is localized intracellular vesicles in the kidney collecting duct cells. AQP7 is expressed in the adipocytes, testis, and kidney. AQP8 is expressed in the kidney, testis, and liver. AQP9 is present in the liver and leukocytes. AQP10 is expressed in the intestine. The diverse and characteristic distribution of aquaporins in the body suggests their important and specific roles in each organ.
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PMID:Aquaporins: water channel proteins of the cell membrane. 1524 1

Chondrocytes exist in an unusual and highly variable ionic and osmotic environment in the extracellular matrix of articular cartilage. Alterations to the ionic and osmotic environment of chondrocytes influence the volume and ionic content of the cells, which, in turn, modifies the rate at which extracellular matrix macromolecules are synthesized and degraded. Thus, regulation of the water and solute content of chondrocytes will profoundly affect their anabolic and catabolic functions. The water content of cells is effectively influenced by the abundance of aquaporin (AQP) water channels. Recent studies have shown that several AQP water channel isoforms are expressed in chondrocytes from Meckel's cartilage, developing teeth and other orofacial tissues. The aim of the present investigation was to determine if chondrocytes from equine articular cartilage express AQP water channels. Polyclonal antibodies to AQP1, AQP2 and AQP3 were used in conjunction with immunohistochemistry, immunoblotting and quantitative flow cytometry to determine if AQP1, AQP2 and AQP3 are expressed in equine articular chondrocytes. Our studies show that AQP1 and AQP3 are expressed by chondrocytes in articular cartilage in situ and in isolated chondrocytes. We found no evidence for expression of AQP2, the vasopressin-regulated water channel in chondrocytes. AQP1 and AQP3 may be involved in the transport of water and small solutes and osmotically active metabolites across the chondrocyte plasma membrane during volume regulatory behaviour. AQP1 may be involved in transporting metabolic water. AQP3 may participate in the transport of glycerol and structurally related molecules.
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PMID:Aquaporin water channels AQP1 and AQP3, are expressed in equine articular chondrocytes. 1530 62


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