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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 436 (1998), S. 814-827 
    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
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  • 2
    ISSN: 1432-2013
    Keywords: Key words MDCK cells ; Hypertonic stress ; NaCl ; Urea ; Organic osmolytes ; Heat shock proteins ; Cell viability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In antidiuresis, the cells of the renal medulla are exposed to high extracellular concentrations of NaCl and urea. Since urea equilibrates with the intracellular compartment and is known to perturb intracellular macromolecules, high urea concentrations may well disturb the structure and function of cell proteins. Two types of organic substances are believed to counteract the adverse effects of high intracellular urea concentrations: specific organic osmolytes of the trimethylamine family [betaine and glycerophosphorylcholine (GPC)], which accumulate in renal medullary cells during prolonged periods of antidiuresis and cytoprotective heat shock proteins (HSPs), the tissue content of two of which (HSPs 27 and 72) is much higher in the inner medulla than in the iso-osmotic renal cortex. To evaluate the contribution of trimethylamines and HSPs to cytoprotection in the presence of high urea concentrations, the effect of HSP induction and osmolyte accumulation prior to exposure to high urea concentrations was examined in Madin-Darby canine kidney (MDCK) cells. Accumulation of organic osmolytes and synthesis of HSP27 and HSP72 was initiated by hypertonic stress (increasing the osmolality of the medium from 290 to 600 mosmol/kg H2O by NaCl addition). Control, non-conditioned cells remained in the isotonic medium for the same period. Upon subsequent exposure to an additional 600 mM urea in the medium for 24 h, 90% of the osmotically conditioned cells but only 15% of non-conditioned cells survived. The HSP72 and trimethylamine contents of the NaCl-conditioned MDCK cells, but not HSP27 content, correlated positively with cell survival. To separate the effects of organic osmolytes and HSP72, chronically NaCl-adapted MDCK cells were returned to isotonic medium for 1 or 2 days, so depleting them of trimethylamine osmolytes. HSP72, with its longer half life, remained elevated. Subsequent exposure of these cells to 600 mM urea in the medium resulted in about 80% survival. These results suggest that in MDCK cells and probably in the renal medulla, HSP72 and perhaps additional protective factors contribute substantially to the resistance against high urea concentrations.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 1091-1095 
    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
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 66 (1988), S. 843-848 
    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
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