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  • 1
    Electronic Resource
    Electronic Resource
    Regulation and localization of organic osmolytes in mammalian kidney (1990)
    Springer
    Journal of molecular medicine 68 (1990), S. 1091-1095 
    Details
    ISSN: 1432-1440
    Keywords: Organic osmolytes ; Rat kidney ; Diabetes insipidus ; Diabetes mellitus ; Hormone treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four organic small molecules belonging to the chemical groups of trimethylamines (betaine and glycerophosphorylcholine) and polyols (sorbitol and inositol) have been shown to act as organic osmolytes in the kidney. When measured along the corticopapillary axis, each exhibits a specific distribution pattern, indicating a specific localization and function. Studying their behaviour under vasopressin treatment in diabetes insipidus rats and after insulin treatment in diabetes mellitus rats confirmed this conclusion: AVP led to a steady increase of sorbitol and glycerophosphorylcholine over 7 days with no effect on inositol levels. Insulin treatment of diabetic rats, on the other hand, decreased sorbitol with a concomitant increase in glycerophosphorylcholine, again without any effect on tubular inositol concentrations. From this and in vitro studies it can be concluded that both hormones act by indirect mechanisms which alter interstitial osmolality. This in turn leads to a change in tubular osmolyte synthesis, uptake and release rates. In addition, the concentrations of the respective precursors glucose and choline influence the formation rates of sorbitol and betaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01798058
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  • 2
    Electronic Resource
    Electronic Resource
    Buchbesprechungen (1991)
    Springer
    Journal of molecular medicine 69 (1991), S. 184-184 
    Details
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01665866
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  • 3
    Electronic Resource
    Electronic Resource
    Cellular osmoregulation in the renal papilla (1988)
    Springer
    Journal of molecular medicine 66 (1988), S. 843-848 
    Details
    ISSN: 1432-1440
    Keywords: Renal papillary cells ; Cell electrolytes ; Osmoadaptation ; Organic osmolytes ; Electron microprobe analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cells of the renal papilla are subject to extreme variations in extracellular tonicity. To obtain more insight into the mechanisms whereby these cells adapt osmotically to these unique environmental conditions, elements were measured in individual cells of the rat renal papilla in antidiuresis and after prolonged furosemide administration. In antidiuresis cell sodium, chloride and potassium concentrations did not differ fundamentally from those observed in tubule cells exposed to isotonic surroundings such as in proximal tubule cells. The marked fall in extracellular electrolyte concentrations induced by furosemide was paralleled by a far less pronounced decline in intracellular sodium, chloride and potassium concentrations. These data indicate that papillary cells achieve osmoadaptation to widely differing extracellular tonicities mainly by varying the intracellular concentrations of osmotically active substances other than inorganic electrolytes. Since high concentrations of organic osmolytes (sorbitol, inositol, glycerophosphorylcholine and other trimethylamines) have been detected in the papilla and since the tissue contents of these compounds have been shown to vary in parallel with urine osmolality, it may be concluded that metabolically inert, organic osmolytes play a dominant role in the osmoregulation of renal papillary cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728945
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  • 4
    Electronic Resource
    Electronic Resource
    A method of preparing single renal tubules for electron microprobe analysis (1983)
    Springer
    Pflügers Archiv 399 (1983), S. 241-242 
    Details
    ISSN: 1432-2013
    Keywords: Single renal tubules ; Electron microprobe analysis ; Cellular concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method is described whereby single renal tubules, incubated in varying incubation media can be captured and prepared for electron microprobe analysis for intracellular sodium, potassium, chloride, phosphorus, magnesium amongst others.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00656723
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  • 5
    Electronic Resource
    Electronic Resource
    Solute composition and heat shock proteins in rat renal medulla (1997)
    Springer
    Pflügers Archiv 434 (1997), S. 117-122 
    Details
    ISSN: 1432-2013
    Keywords: Key words Organic osmolytes ; Urea ; Intracellular electrolytes ; Heat shock proteins ; HSP25 ; HSP72 ; Osmoregulation ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The high content of heat shock proteins (HSPs) 25 and 72 in the hyperosmotic inner medulla of the concentrating kidney has been ascribed to the high NaCl and urea concentrations in this kidney zone. To assess the effects of variations in the composition of solutes in the renal medulla on the intrarenal distribution of HSPs, rats were fed either a high- or low-Na diet for 3 weeks. These diets result in greatly differing urine and inner medullary solute composition. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot techniques were used to analyse HSP25 and HSP72 in the cortex, outer medulla and inner medulla. In addition, the amounts of organic osmolytes (sorbitol, myo-inositol, betaine and glycerophosphorylcholine) and urea in the tissue were determined by high-performance liquid chromatography. Intra- and extracellular electrolyte concentrations at the papillary tip were measured by electron microprobe analysis. In the high-Na group, urine osmolality was about 1000 mosmol/kg lower than in rats fed a low-Na diet, due to lower urea concentrations. The sum of urine sodium and potassium concentrations, however, did not differ between the two groups. Neither in the outer nor in the inner medulla was the sum of the concentrations of organic osmolytes affected by the dietary treatment. The sum of sodium, potassium and chloride concentrations did not differ between the two experimental groups, neither in the interstitial nor in the intracellular compartments. However, the urea content and the amounts of HSP25 and HSP72 were significantly lower in the inner medulla of the group of rats fed a high-Na diet. Our results suggest that urea participates in the regulation of the medullary levels of the HSPs and that both HSP25 and HSP72 are components of mechanisms protecting medullary cells against the deleterious effects of high urea concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050371
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of long-term changes in medullary osmolality on heat shock proteins HSp25, hsp60, HSP72 and HSP73 in the rat kidney (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 705-712 
    Details
    ISSN: 1432-2013
    Keywords: Key words Diuresis/antidiuresis ; Osmotic stress ; HSP25 ; HSP60 ; HSP72 ; HSP73 ; Transcription ; Translation ; Medullary hypertonicity ; Phosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of diuresis and antidiuresis on the expression of heat shock proteins (HSP) 25, 60, 72 and 73 in the renal cortex and outer and inner medulla of Wistar rats was analysed. Medullary osmolality was reduced by long-term diuresis (3% sucrose in the drinking water for 3 weeks) and subsequently enhanced by transition to a concentrating state by giving normal drinking water again in combination with deamino-D-arginine vasopressin (dDAVP) for 5 days. Western blot analyses revealed that neither HSP73 nor HSP60 was influenced by any treatment. The HSP72 level in the medulla was markedly reduced (50%) when osmolality was lowered and increased when tonicity was high. RNAse protection assays showed that the effects on HSP72 are parallelled in general by changes in HSP72 mRNA. While levels of HSP25 were not influenced, isoelectric focusing revealed that the degree of phosphorylation of outer and inner medullary HSP25 increased following both treatments. It thus seems that HSP73 and HSP60 are not directly involved in the long-term adaptation to varying medullary osmolalities. The correlation between changes in osmolality and amounts of the major stress-inducible HSP72 in the medulla implies that medullary hypertonicity is stressful for kidney cells. Furthermore, adaptation to pronounced changes in the osmolality of the environment most likely involves phosphorylation of HSP25.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050572
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  • 7
    Electronic Resource
    Electronic Resource
    Cellular response to osmotic stress in the renal medulla (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 814-827 
    Details
    ISSN: 1432-2013
    Keywords: Key words Antidiuresis ; Diuresis ; Heat shock proteins ; Ionic strength ; Organic osmolytes ; Osmotic stress ; Renal medulla
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cells of the renal medulla, which are exposed under normal physiological conditions to widely fluctuating extracellular solute concentrations, respond to hypertonic stress by accumulating the organic osmolytes glycerophosphorylcholine (GPC), betaine, myo-inositol, sorbitol and free amino acids. Increased intracellular contents of these osmolytes are achieved by a combination of increased uptake (myo-inositol and betaine) and synthesis (sorbitol, possibly GPC), decreased degradation (GPC) and reduced osmolyte release. In the medulla of the concentrating kidney, accumulation of organic osmolytes, which do not perturb cell function even at high concentrations, allows the maintenance of ”normal” intracellular concentrations of inorganic electrolytes. Adaptation to decreasing extracellular solute concentrations, e.g. diuresis, is achieved primarily by activation of pathways allowing the efflux of organic osmolytes, and secondarily by inactivation of production (sorbitol) and uptake (betaine, myo-inositol) and stimulation of degradation (GPC). Apart from modulation of the osmolyte content, osmolality-dependent reorganization of the cytoskeleton and expression of specific stress proteins (heat shock proteins) may be further, as yet poorly characterized, components of the regulatory systems involved in the adaptation of medullary cells to osmotic stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050710
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  • 8
    Electronic Resource
    Electronic Resource
    Expression of Na+/Cl–/betaine and Na+/myo-inositol transporters, aldose reductase and sorbitol dehydrogenase in macula densa cells of the kidney (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 807-809 
    Details
    ISSN: 1432-2013
    Keywords: Key words Aldose reductase ; In situ hybridization ; Macula densa ; Na+/Cl ; /betaine cotransporter ; Na+/myo-inositol cotransporter ; Osmolytes ; Sorbitol dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has been suggested that macula densa cells may be exposed to hyperosmotic stress. Since chronic exposure to hypertonic stress causes the amount of intracellular organic osmolytes to increase, the expression of transporters and enzymes that participate in the intracellular accumulation of organic osmolytes was examined using non-radioactive in situ hybridization in the macula densa region of control rats and furosemide-treated animals. Both the sodium- and chloride-dependent betaine transporter (BGT) and sodium-dependent myo-inositol transporter (SMIT) were expressed preferentially in macula densa cells and for both mRNAs the signal intensity was visibly reduced by furosemide. The enzymes aldose reductase (which mediates the conversion of glucose to sorbitol) and sorbitol dehydrogenase (which converts sorbitol into fructose) were expressed not only in macula densa cells but also in the surrounding tubular cells, and the expression was insensitive to furosemide. Thus it remains unclear whether the expression of BGT and SMIT is related to a putative hypertonic juxtaglomerular region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050707
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  • 9
    Electronic Resource
    Electronic Resource
    Inhibition of NaCl-induced heat shock protein 72 expression renders MDCK cells susceptible to high urea concentrations (1999)
    Springer
    Pflügers Archiv 437 (1999), S. 611-616 
    Details
    ISSN: 1432-2013
    Keywords: Key words Antisense ; Heat shock proteins ; Hypertonic stress ; MDCK cells ; Transfection ; Urea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Exposure of Madin-Darby canine kidney (MDCK) cells to elevated extracellular NaCl concentrations is associated with increased heat shock protein 72 (HSP72) expression and improved survival of these pretreated cells upon exposure to an additional 600 mM urea in the medium. To establish a causal relationship between HSP72 expression and cell protection against high urea concentrations, two approaches to inhibit NaCl-induced HSP72 synthesis prior to exposure to 600 mM urea were employed. First, the highly specific p38 kinase inhibitor SB203580 was added (100 µM) to the hypertonic medium (600 mosm/kg H2O by NaCl addition, 2 days of exposure), which significantly reduced HSP72 mRNA abundance and HSP72 content. Survival of these cells after a 24-h urea treatment (600 mM) was markedly curtailed compared with appropriate controls. Second, a pcDNA3-based construct, containing 322 bases of the HSP72 open reading frame in antisense orientation and the geneticine resistance gene, was transfected into MDCK cells. Clones with strong inhibition of HSP72 synthesis and others which express the protein at normal levels (comparable to nontransfected MDCK cells) after heat shock treatment or hypertonic stress were established. When these transformants were subjected to hypertonic stress for 2 days prior to exposure to an additional 600 mM urea for 24 h, cell survival was significantly reduced in those clones in which HSP72 expression was strongly inhibited. These results provide further evidence for the protective function of HSP72 against high urea concentrations in renal epithelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050824
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  • 10
    Electronic Resource
    Electronic Resource
    Influence of NaCl, urea, potassium and pH on HSP72 expression in MDCK cells (1999)
    Springer
    Pflügers Archiv 439 (1999), S. 195-200 
    Details
    ISSN: 1432-2013
    Keywords: Heat shock protein Medullary solutes Renal epithelial cells Synergistic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The renal inner medulla is characterised by elevated extracellular concentrations of NaCl, urea, potassium and hydrogen ions, an environment that may affect cell viability negatively. High amounts of HSP72, a stress protein allowing cells to resist harmful situations, are also observed in this region. The present study examined HSP72 induction by various medullary stress factors, individually or in combination, in MDCK cells, a renal epithelial cell line expressing characteristics of the medullary collecting duct. MDCK cells were incubated for 3 days in media containing elevated concentrations of NaCl, urea, potassium and hydrogen ions individually or in combination. HSP72 mRNA and protein expression were determined by Northern and Western blot analyses, respectively. HSP72 expression was enhanced moderately by addition of 50 mM NaCl to normal medium at pH 7.4 but enhanced strongly when added at pH 6.5. The latter degree of HSP72 induction was comparable to that observed when 150 mM NaCl was added at pH 7.4. In normal medium (pH 7.4) containing 300 mM urea, MDCK HSP72 expression was not different from controls. In contrast, urea-induced HSP72 expression was clearly evident when medium pH was lowered to 6.5. Potassium at 20 or 40 mM induced HSP72 only slightly. These results indicate that expression of HSP72 in renal epithelial cells is regulated synergistically by NaCl, urea and pH. Since HSP72 is only slightly induced by increased potassium, this probably reflects the changes in medium osmolality rather than a specific effect of potassium. The high medullary HSP72 content observed even in diuresis may be due to co-operative effects of medullary solutes on HSP72 expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004249900164
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