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)

To clarify the role of the sugar polyols, sorbitol and myo-inositol, in cerebral cell volume regulation, we studied the effect of sorbinil, an inhibitor of aldose and aldehyde reductase, on the size of the cerebral water compartments in rats with hypernatremia, hyponatremia and normonatremia. Experimental animals were pretreated with sorbinil, while comparison rats received the drug vehicle. Rats were made hypernatremic for 96 h by water deprivation and injections of hypertonic saline, while hyponatremia was provoked over 48 h by daily administration of 5% dextrose in water and vasopressin. Sorbinil treatment was continued throughout the hyper- and hyponatremic periods. The severity of hypernatremia and hyponatremia was similar in sorbinil-treated and corresponding vehicle-treated rats. Brain electrolyte content and the size of the cerebral intracellular water compartment were comparable in sorbinil-treated rats vs. controls under hypernatremic and hyponatremic conditions. Sorbinil reduced the cerebral sorbitol content by approximately 50%, irrespective of the serum Na+ concentration. In contrast, sorbinil had no effect on brain myo-inositol content which rose by 114% during chronic hypernatremia (P less than 0.0001). Cerebral levels of myo-inositol did not decline in hyponatremic rats. We conclude that (1) sorbitol is not an essential cerebral osmolyte; and (2) myo-inositol is involved in the maintenance of brain cell volume during severe hypernatremia but not under hyponatremic conditions.
 ...
PMID:The role of polyols in cerebral cell volume regulation in hypernatremic and hyponatremic states. 190 5

The renal response to changes in hydration includes variation in intracellular sorbitol, a major inner medullary osmolyte. To examine the mechanism for changes in net sorbitol production, we measured activities of enzymes regulating sorbitol production (aldose reductase) and degradation (sorbitol dehydrogenase) in untreated, water diuretic, and antidiuretic (water restriction and/or vasopressin administration) rats. Collecting duct segments dissected from collagenase-treated kidneys of Sprague-Dawley rats were divided into outer medullary and three distinct inner medullary regions. Aldose reductase activity increased during antidiuresis and decreased during diuresis. In contrast, sorbitol dehydrogenase activity was very low during antidiuresis and increased during diuresis. These changes in enzyme activity were found after 3 days, but not after 1 day, of water diuresis/antidiuresis. Enzyme activity changed only in the deepest 50% of the inner medullary collecting duct. Thus, there is coordinated regulation of aldose reductase and sorbitol dehydrogenase activities so that (a) during water diuresis, aldose reductase activity decreases while sorbitol dehydrogenase activity increases; and (b) during antidiuresis (water restriction and/or vasopressin administration), aldose reductase activity increases while sorbitol dehydrogenase activity remains low. We conclude that long-term osmoregulation in response to physiologic stimuli involves both aldose reductase and sorbitol dehydrogenase activities in rat terminal inner medullary collecting duct segments.
 ...
PMID:Coordinated response of renal medullary enzymes regulating net sorbitol production in diuresis and antidiuresis. 212 8

The regulation of mRNA for aldose reductase, sorbitol dehydrogenase, and the Na+/Cl-/taurine cotransporter was studied with three in vivo models in which urinary concentration is reduced: Sprague-Dawley rats undergoing a water diuresis or fed a low-protein diet or Brattleboro rats. In Sprague-Dawley rats, 3 days of water diuresis reduced inner medullary aldose reductase mRNA abundance 6.5-fold compared with untreated rats, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged. When water diuretic rats were acutely deprived of water, urine osmolality increased significantly after 4 h but aldose reductase mRNA did not increase until 12 h. Heat shock protein-70 mRNA was not increased by water deprivation. Second, in rats fed a low-protein diet for 3 wk, aldose reductase mRNA increased two-fold, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged. Finally, in Brattleboro rats, urine osmolality and levels of aldose reductase and taurine cotransporter mRNA increased in response to 1 day of water deprivation, whereas sorbitol dehydrogenase mRNA was unchanged. Administering vasopressin (1 U/day) to Brattleboro rats for 8 days also increased urine osmolality and aldose reductase mRNA but did not alter sorbitol dehydrogenase or taurine cotransporter mRNA. This result is consistent with the hypothesis that changes in urine osmolality induce changes in aldose reductase mRNA abundance that are independent of vasopressin. It was concluded that, in rat inner medulla: (1) aldose reductase mRNA abundance varies with changes in water balance or dietary protein, whereas sorbitol dehydrogenase and taurine cotransporter mRNA do not; and (2) heat shock protein-70 mRNA abundance is not increased during acute osmotic stress.
 ...
PMID:Regulation of aldose reductase, sorbitol dehydrogenase, and taurine cotransporter mRNA in rat medulla. 762 95

For the purpose of clarifying the role of vasopressin V1 and V2 receptors in osmolyte accumulation, we determined the effects on the inner medullary osmolyte content of the administration of orally active vasopressin V1 and/or V2 receptor antagonists OPC-21268 (i.e., 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)- 3,4-dihydro-2(1H)-quinolinone) and OPC-31260 (i.e., 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tet rah ydro-1H- benzazepine] under a condition of maximal urine concentration achieved by water deprivation for 4 days. Taurine content increased significantly with the use of the V2 antagonist, irrespective of the use of the V1 antagonist. Inner medullary betaine content decreased with the administration of the V1 antagonist, irrespective of the administration of V2 antagonist. The administration of either the V1 or V2 antagonist alone did not affect sorbitol content, aldose reductase activity, or aldose reductase mRNA abundance in renal inner medulla. However, the combined administration of the V1 and V2 antagonists decreased all of these significantly. Myo-inositol content was not affected by the administration of the V1 or V2 antagonists. Glycerophosphorylcholine content was decreased with the use of the V2 antagonist, irrespective of the use of the V1 antagonist, and this effect paralleled urine osmolality. In conclusion, the individual organic osmolytes responded differently to the antagonists of vasopressin V1 and/or V2 receptors. The mechanisms linked to vasopressin V1 and/or V2 receptors appeared to modulate the accumulation of some organic osmolytes in the inner medulla. Aldose reductase mRNA abundance and sorbitol accumulation in the inner medulla appeared to be mediated through either V1 or V2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Organic osmolytes in rat renal inner medulla are modulated by vasopressin V1 and/or V2 antagonists. 804 55

We reported that feeding rats 8% protein for 4 wk induces two new urea transport processes in initial inner medullary collecting ducts (IMCD); neither is present in rats fed 18% protein. In this study, we measured the time course of induction of these transporters in perfused initial IMCD segments from rats fed 8% protein. Net urea flux was induced after 3 wk, whereas vasopressin-stimulated passive urea permeability (P(urea)) was induced after 2 wk. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) significantly increased P(urea)); adding vasopressin did not increase P(urea) further. In fact, there was no difference in vasopressin-stimulated cAMP production in initial or terminal IMCD segments from rats fed 18% or 8% protein, suggesting that the adaptive response was not due to increased cAMP production. Glucagon did not change cAMP production or P(urea). Specificity of the response was suggested because neither aldose reductase nor sorbitol dehydrogenase activity changed with feeding 8% protein. Thus 1) in initial IMCD segments, vasopressin-stimulated P(urea) is induced after 2 wk, but net urea flux requires 3 wk of feeding 8% protein; 2) this adaptation is not solely due to a higher rate of cAMP production; and 3) specificity of the adaptive response is suggested because activities of enzymes responding to decreases in concentrating ability are unchanged. These results suggest that two distinct urea transporters may be involved in the adaptation to a low-protein diet.
 ...
PMID:Protein restriction sequentially induces new urea transport processes in rat initial IMCD. 820 59

The effect of changes in medullary extracellular tonicity on mRNA expression for aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl-/betaine (BGT) and Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using Northern blot analysis and non-radioactive in situ hybridization in four groups of rats: controls, acute diuresis (the loop diuretic furosemide was administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of diuresis followed by 24 h deamino-Cys1, d-Arg8 vasopressin (dDAVP)]. Acute administration of the loop diuretic furosemide significantly reduced AR, SMIT and BGT gene expression in the inner and outer medulla compared with controls. Administration of dDAVP to chronically diuretic rats raised the expression of these three mRNAs in the inner but not the outer medulla compared with the chronically diuretic rats. None of these alterations in medullary tonicity significantly changed SDH expression. The in situ hybridization studies showed AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial cells of the outer and inner medulla. The various cell types (epithelial, endothelial and interstitial cells) differed in their expression pattern and intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded uniformly to a decrease in extracellular tonicity with a reduction, and to an increase with enhancement of their AR, BGT and SMIT expression.
 ...
PMID:Expression of aldose reductase, sorbitol dehydrogenase and Na+/myo-inositol and Na+/Cl-/betaine transporter mRNAs in individual cells of the kidney during changes in the diuretic state. 992 66

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.
 ...
PMID:Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney. 1487 80

Mice that lack the aquaporin-1 gene (AQP1) lack a functional countercurrent multiplier mechanism, fail to concentrate the inner medullary (IM) interstitium, and present with a urinary concentrating defect. In this study, we use DNA microarrays to identify the gene expression profile of the IM of AQP1 null mice and corresponding changes in gene expression resulting from a loss of a hypertonic medullary interstitium. An ANOVA analysis model, CARMA, was used to isolate the knockout effect while taking into account experimental variability associated with microarray studies. In this study 5,701 genes of the possible approximately 12,000 genes on the array were included in the ANOVA; 531 genes were identified as demonstrating a >1.5-fold up- or downregulation between the wild-type and knockout groups. We randomly selected 35 genes for confirmation by real-time PCR, and 29 of the 35 genes were confirmed using this method. The overall pattern of gene expression in the AQP1 null mice was one of downregulation compared with gene expression in the renal medullas of the wild-type mice. Heat shock proteins 105 and 94, aldose reductase, adenylate kinase 2, aldolase B, aldehyde reductase 6, and p8 were decreased in the AQP1 null mice. Carboxylesterase 3, matrilin 2, lipocalin 2, and transforming growth factor-alpha were increased in IM of AQP1 null mice. In addition, we observed a loss of vasopressin type 2 receptor mRNA expression in renal medullas of the AQP1 null mice. Thus the loss of the hyperosmotic renal interstitium, due to a loss of the concentrating mechanism, drastically altered not only the phenotype of these animals but also their renal medullary gene expression profile.
 ...
PMID:Renal medullary gene expression in aquaporin-1 null mice. 1550 45

Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of TonEBP target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/tonicity of the renal medullary interstitium as a result of inhibition of active sodium transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not affect TonEBP or renal function. Whereas expression of sodium transporters was altered, the medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of TonEBP and overt nephrotoxicity. The downregulation of TonEBP involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters-sodium/potassium/chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal medullary interstitium.
 ...
PMID:Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A. 1720 15

Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health.
 ...
PMID:Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease. 2608 40


1 2 Next >>