Biomedical subjects

F X Beck

Publications and source records attributed to F X Beck.

At least 37 records · Page 2Linked to original sources

PubMed1997

Endothelin-1 potently stimulates chloride secretion and inhibits Na(+)-glucose absorption in human intestine in vitro.

1. Serosally added synthetic endothelin-1 (ET-1) increased short-circuit current (Isc) across isolated muscle-stripped human colonic mucosa in vitro. Bumetanide inhibited Isc responses, indicating that ET-1 stimulates electrogenic Cl- secretion. 2. In isolated human jejunal mucosa, ET-1 exhibited a concentration-dependent dual action. At low concentrations it induced rapid increases in Isc and these were inhibited by bumetanide. At a higher concentration (0.1 microM), ET-1 provoked a drastic and progressive decrease in Isc below the baseline value. 3. Pretreatment with phlorizin or omission of glucose from the Krebs-Ringer solution at the apical (luminal) side of the jejunal mucosa prevented the decreases in Isc evoked by ET-1, suggesting that the peptide inhibits the glucose-coupled electrogenic Na+ absorption. Indeed, flux experiments with D-[14C]glucose demonstrated that ET-1 decreases jejunal glucose absorption by approximately 80% within 30 min. 4. Electron microprobe analyses of cryosections of human jejunum showed that ET-1 (0.1 microM) evokes a significant decrease in intracellular Na+ concentrations of villus (not crypt) epithelial cells, suggesting that the peptide attenuates apical Na(+)-glucose entry by reducing the activity of the Na(+)-glucose cotransporter, SGLT1. 5. In the presence of tetrodotoxin (TTX), ET-1-induced Cl- secretion was significantly reduced, in both human jejunal and colonic mucosa. However, the inhibitory effect on jejunal Na(+)-glucose absorption was not affected by TTX. 6. ET-1 increases electrogenic Cl- secretion across human intestinal mucosa in vitro. This effect is mediated in part via the activation of enteric nerves. Responses of the human jejunal mucosa to high ET-1 concentrations exhibit a second component, namely the rapid inhibition of electrogenic Na(+)-glucose absorption, which might be mediated by an inhibition of the transport activity of SGLT1. This effect is independent from neuronal mediators. Our results suggest different cellular action sites for ET-1 in human small and large intestine.

Absorption↗

PubMed1997

The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones.

Induction of heat shock proteins (HSPs) following cell injury contributes to the protection of vital cell functions. It was, therefore, of interest to study the effects of transient renal ischaemia on the abundance and distribution of two HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of the rat kidney immediately after 60 min of ischaemia followed by varying periods of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding zones of the contralateral control kidney. This initial decrease in supernatant HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM, reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively, than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25 contents had not completely normalised in CX, but had reached control levels in OM. In IM, the HSP25 content remained below control throughout the entire reperfusion period. HSP72 (supernatant) was below the detection limit in the CX of the control kidney. Similar to the level of HSP25, that of HSP72 was also markedly lower in OM and IM immediately after ischaemia. The intrarenal distribution of HSP72 and the sequence of zonal changes in HSP72 contents were similar to those observed for HSP25. These results are compatible with the view that, during ischaemia and the initial reperfusion period, HSP25 migrates from the cytoplasmic compartment (supernatant) into the nucleus and/or associates with cytoskeletal structures. The observation that both HSP25 and HSP72 are transiently induced in CX and OM, but not in IM, may be explained by the fact that, while all kidney cells are exposed to ischaemic stress, only inner medullary cells experience a major postischaemic attenuation of osmotic stress.

Animals↗

PubMed1997

Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis.

The roles of elevated cell sodium concentrations and the angiotensin-aldosterone system (AAS) in the structural and functional adaptation of the distal tubule and collecting duct system to a chronic increase of sodium delivery were examined using electron microprobe and quantitative morphologic/stereologic analyses. Studies were performed on rats given the loop diuretic torasemide acutely (20 min) or chronically (12 days), either alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing cells of the distal tubule and cortical collecting duct-that is, in distal convoluted tubule (DCT), connecting tubule (CNT) and principal cells-an acute increase in sodium delivery caused a significant rise in intracellular sodium concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase activity. The elevated cell sodium concentrations returned to, or close to, control values during chronic torasemide treatment. Intracellular rubidium concentrations, measured after a 30-second rubidium exposure, were not different from controls in DCT and CNT cells but were still higher in principal cells. Since, however, the distribution space for rubidium was significantly increased in chronic torasemide animals, rubidium uptake, and hence Na,K-ATPase activity, must have increased in proportion to cell volume in DCT and CNT cells, but more than proportionately in principal cells. When ACE was inhibited during chronic torasemide, the epithelial volume of DCT and cortical collecting duct (CCD) was increased mainly by lengthening and not, as was the case in rats given torasemide alone, by thickening of the tubule wall. Adaptation of the proximal tubule exclusively by lengthening was not affected by inhibition of the ACE. These data indicate that changes in cell ion composition may participate in initiating cell processes leading to adaptation of distal nephron segments to chronically increased salt delivery. Inhibition of the ACE reverses the torasemide-induced increase in apparent Na pump density in principal cells and seems to shift the relationship between hypertrophy and hyperplasia noted in DCT and CCD after chronic torasemide in favor of hyperplasia.

Aldosterone↗

PubMed1996

Heat shock proteins HSP25, HSP60, HSP72, HSP73 in isoosmotic cortex and hyperosmotic medulla of rat kidney.

The distribution of heat shock proteins (HSP) HSP60, HSP73, HSP72 and HSP25 in the isoosmotic cortex and the hyperosmotic medulla of the rat kidney was investigated using Western blot analysis and immunohistochemistry. HSP73 was homogeneously distributed throughout the whole kidney. The level of HSP60 was high in the renal cortex and low in the medulla. HSP25 and HSP72 were present in large amounts in the medulla. Only low levels of HSP25 and almost undetectable amounts of HSP72 were found in the cortex. HSP25 exists in one nonphosphorylated and several phosphorylated isoforms. Western blot analysis preceded by isoelectric focussing showed that HSP25 predominates in its nonphosphorylated form in the outer medulla but in its phosphorylated form in cortex and inner medulla. Although this intrarenal distribution pattern was not changed during prolonged anaesthesia (thiobutabarbital sodium), a shift from the nonphosphorylated to the phosphorylated isoforms of HSP25 occurred in the medulla. The characteristic intrarenal distribution of the constitutively expressed HSPs (HSP73, HSP60, HSP25) may reflect different states of metabolic activity in the isoosmotic (cortex) and hyperosmotic (medulla) zones of the kidney. The high content of inducible HSP72 in the medulla most likely is a consequence of the osmotic stress imposed upon the cells by the high urea and salt concentrations in the hyperosmotic medullary environment.

Anesthetics↗

PubMed1996

Ketoconazole inhibits organic osmolyte efflux and induces heat shock proteins in rat renal medulla.

Although ketoconazole (KC) is known to inhibit the cellular efflux of organic osmolytes in vitro, it is not known whether this effect can also be shown in vivo. Inhibition of osmolyte efflux by KC would impair osmotic adaptation and result in stress to the cells of the renal medulla when extracellular osmolality falls. Stress-inducible heat shock proteins (HSPs) may also participate in this response to osmotic stress. The aim of the present study was thus to establish whether KC inhibits organic osmolyte efflux from the cells of the renal medulla in vivo in response to a furosemide diuresis, and to establish whether HSPs are involved. A 20-minute furosemide infusion reduced urine osmolality and medullary urea content in control and KC-treated rats similarly. However, the efflux of methylamines (glycerophosphorylcholine, betaine) and polyols (myo-inositol, sorbitol) was attenuated in KC-treated rats while the efflux of amino acids was not significantly affected. Phosphorylation of HSP25 after the 20-minute furosemide diuresis was increased in KC rats. With continuing diuresis this returned to control levels after three hours. While short-term (up to 3 hr) diuresis did not alter the absolute amounts of HSPs in the renal medulla, long-term (24 or 48 hr) diuresis was associated with significantly increased amounts of HSP25 and HSP72 in KC-treated rats compared with control. These results suggest that KC inhibits the efflux of methylamines and polyols, thus impeding osmoadaptation of renal medullary cells during the onset of diuresis. This situation apparently increases the osmotic stress experienced by the cells of the renal medulla and provokes expression of HSP25 and HSP72.

Animals↗

PubMed1995

Ischemia-induced changes in cell element composition and osmolyte contents of outer medulla.

The effect of 60 minutes of ischemia and subsequent reflow on cell electrolyte and water homeostasis in the rat renal outer medulla was studied by determining sodium, potassium, chloride and phosphorus concentrations and dry weights in individual tubule cells using electron microprobe analysis. HPLC was employed to measure glycerophosphorylcholine, betaine, inositol and sorbitol, as well as several free amino acids in cortical and outer medullary tissue. Ischemia caused cell sodium and chloride concentrations to rise and cell potassium and phosphorus concentrations and cell dry weights to fall. These changes were most pronounced in the proximal straight tubule (PST) cells, less in thick ascending limb (MAL) and outer medullary collecting duct (OMCD) dark cells and barely noticeable in OMCD light cells. Except for some PST cells these changes were almost completely reversed 60 minutes after reintroducing blood flow. After 24 hours of reperfusion the number of PST cells exhibiting deranged electrolyte homeostasis was greatly increased. The contents of glycerophosphorylcholine, betaine or inositol in the cortex and outer medulla were not affected immediately following ischemia. After 24 hours of reperfusion, the cortical contents of osmolytes were still normal, while outer medullary contents were reduced. Except for low glycine contents, the ischemia-induced changes in amino acid contents were reversed after 24 hours of reflow in the cortex, whereas in the outer medulla aspartate, glycine and taurine contents were diminished. These results indicate increasing manifestation of PST cell injury in the reflow period. The defective re-accumulation of organic osmolytes and free amino acids in the outer medulla during reflow may reflect reduced interstitial tonicities, or may be due to inappropriate cellular uptake, synthesis or/and release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effects of chronic hyperfiltration on proximal tubule bicarbonate transport and cell electrolytes.

The compensatory response to unilateral nephrectomy (UNX) was investigated by a combination of renal clearance, microperfusion, electron microprobe, and morphological techniques. Filtration rate was significantly elevated 21 days following UNX and associated with a marked stimulation of bicarbonate and fluid absorption in the proximal tubule. Analysis of kinetic data of bicarbonate transport demonstrated strong flow-dependent activation of bicarbonate absorption in both control and experimental condition. The bicarbonate level at which half-saturation (apparent Kd) of transport occurred decreased uniformly at higher flow rates, but maximal transport rates (apparent Vmax) in the proximal tubule doubled in the remnant kidney. The flow dependence of bicarbonate transport in control and experimental conditions can be explained by an apparent unstirred layer effect modifying radial bicarbonate gradients in the tubule. Both Na/H-exchange and electrogenic H secretion contribute to bicarbonate absorption, but only Na/H-exchange increased significantly in proximal tubules of UNX rats. Cell ion concentrations after UNX were unchanged in cortical tubules, consistent with proportionately enhanced apical and basolateral ion transport. Proximal tubule cell rubidium concentration measured after a 30-second rubidium infusion as an index of basolateral Na,K-ATPase activity was unchanged in UNX rats. Inasmuch as cell volume increased significantly (25%), these data are consistent with a proportionate and similar stimulation of rubidium uptake and Na,K-ATPase activity.

Animals↗

PubMed1995

Restoration of urine concentrating ability and accumulation of medullary osmolytes after chronic diuresis.

Restoration of urine osmolality (Uosm) and medullary osmolyte contents after chronic diuresis was studied in rats infused for 6 days with furosemide and subsequently given the vasopressin analogue, 1-desamino-8-D-arginine vasopressin (DDAVP). Papillary tip intra- and extracellular electrolyte concentrations were measured by electron microprobe analysis, tissue contents of methylamines (glycerophosphorylcholine, betaine), polyols (myo-inositol, sorbitol), and several amino acids in different kidney zones by high-performance liquid chromatography. Administering DDAVP continuously after diuresis increased Uosm from (means +/- SE) 348 +/- 8 to 1,265 +/- 127 after 1 day and 2,485 +/- 186 mosmol/kgH2O after 3 days. The sum of all osmolytes at the papillary tip rose from 309.2 +/- 28.9 to 690.9 +/- 105.8 and 1,282.8 +/- 21.0 mmol/kg protein after days 1 and 3, respectively. Although interstitial tonicity (sum of Na, Cl, and K concentrations) was increased by 116 and 223% after 1 and 3 days DDAVP, intracellular tonicity was similar in chronic diuresis and following 1 or 3 days DDAVP. Coadministration of DDAVP with betaine, myo-inositol, and choline ("osmolyte treatment") did not accelerate the restoration of Uosm but caused significantly higher contents of osmolytes (except myo-inositol) in inner medulla and/or papilla after 3 days. In a minority of animals, restoration of Uosm and reaccumulation of medullary osmolytes were impeded in both DDAVP- and DDAVP/osmolyte-treated rats. These data indicate that, after chronic diuresis, accumulation of organic osmolytes and restoration of Uosm proceed in parallel. Capacity for transport and/or synthesis of organic osmolytes, rather than their availability, appear to limit reaccumulation on the first day of recovery. By the third day, delivery of some osmolytes or their precursors may limit the restoration of medullary osmolyte content. The failure of some rats to attain sufficient concentrating ability within this time period may be related to deficient reaccumulation of medullary osmolytes.

Amino Acids↗

PubMed1994

Electron microprobe analysis of electrolytes in whole cultured epithelial cells.

Microprobe analysis was used to determine electrolyte contents in whole epithelial sheets of A6 cells and to investigate the most critical points of this method. Analysis of dextran standard sections of different thickness revealed that low accelerating voltages of about 10 kV are best suited for whole freeze-dried cells on thick supports, since 5 microM thick sections are not penetrated by 10 kV electrons. Washing of A6 cells for 10 sec with distilled water led to cell swelling of about 40%, but the molar concentration ratios and the concentrations per dry weight (dw) were not altered. Washing for 60 sec with distilled water caused a further increase in cell volume (120%) and loss of cellular K and Cl (90 mmol/kg dw). Washing with isotonic NH4- acetate led to a loss of cell Cl already after 10 sec. To characterize the Na transport compartment, A6 cells cultured on permeable supports were washed for 5 sec with distilled water, freeze-dried, and analyzed. Inhibition of transepithelial Na transport by ouabain increased Na/P from 0.15 +/- 0.07 to 0.75 +/- 0.03 and Cl/P from 0.21 +/- 0.001 to 0.38 +/- 0.003 while K/P decreased from 0.83 +/- 0.08 to 0.32 +/- 0.03. The changes in cell Na and K contents can be explained by K/Na exchange; the increase in Cl content indicates some cell swelling. Since the ouabain-induced changes could be prevented by apical amiloride, the apical membrane provides the most important pathway for Na entry in A6 cells.

Animals↗

PubMed1994

Loop diuretics affect transcellular electrolyte transport in cells of the distal convoluted tubule.

Although loop diuretics act preferentially on sodium chloride absorption in the thick ascending limb of the loop of Henle in the nephron, high concentrations of some loop diuretics also impair sodium absorption in the distal convoluted tubule (DCT). To characterize further the inhibitory effect of these agents on sodium absorption in the DCT, the action of torsemide and furosemide on cell sodium, chloride and potassium concentrations was examined in individual DCT cells of the kidney cortex and also, for comparison, in proximal convoluted tubule cells. In addition, initial cell uptake rates of rubidium, an index of in vivo Na+/K(+)-ATPase activity, were studied. Both diuretics caused a significant reduction of intracellular sodium concentration and rubidium uptake in DCT cells but not in connecting tubule, principal, intercalated or proximal tubule cells. These findings are consistent with the concept that both diuretics reduce transcellular sodium absorption in DCT cells by impairing sodium entry across the apical cell membrane and, as a consequence, sodium extrusion by primary active Na+/K+ (Rb+) exchange across the basolateral membrane.

Animals↗

PubMed1993

Transcellular sodium transport and basolateral rubidium uptake in the isolated perfused cortical collecting duct.

The relation between transcellular Na+ absorption, intracellular Na+ concentration and Na+/K(+)-ATPase activity (the last estimated by the rubidium uptake across the basolateral cell membrane) was examined in the different cell types of the rabbit cortical collecting duct (CCD). Experiments were performed on isolated perfused CCD in which Na+ absorption was varied by perfusing the tubule with solutions containing different Na+ concentrations (nominally Na(+)-free, 30 mM and 144 mM). Experiments were terminated by shock-freezing the tubules during perfusion. Precisely 30 s before shock-freezing, the K+ in the bathing solution was exchanged for Rb+. Intracellular element concentrations, including Rb+, were determined in freeze-dried cryosections of the tubules using energy-dispersive X-ray analysis. Increasing Na+ concentration in the perfusion solution caused significant rises in intracellular Na+ concentration and Rb+ uptake of principal cells. Principal cell Na+ and Rb+ concentrations were 7.8 +/- 0.9 and 7.0 +/- 0.8 mmol/kg wet weight respectively, when the perfusion solution was Na(+)-free, 10.1 +/- 0.7 and 11.6 +/- 0.6 mmol/kg wet weight with 30 mM Na+ in the perfusion solution, and 14.5 +/- 1.5 and 14.9 +/- 0.9 mmol/kg wet weight with 144 mM Na+ in the perfusion solution. In contrast, a comparable relationship between lumen Na+ concentration, intracellular Na+ concentration and basolateral Rb+ uptake was not seen in intercalated cells. These results support the notion that principal, but not intercalated, cells are involved in transepithelial Na+ absorption. In addition, the data demonstrate that apical Na+ entry and basolateral Na+/K(+)-ATPase activity are closely coupled in principal cells of the rabbit CCD.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1993

Osmotic adaptation of renal medullary cells during transition from chronic diuresis to antidiuresis.

The cells of the renal medulla adapt osmotically to high extracellular tonicities by high concentrations of organic osmolytes. Intracellular accumulation of these substances is, however, relatively slow. The aim of the present study was to assess the effect of an abrupt rise in extracellular tonicity on intracellular osmotically active substances after prior reduction of medullary contents of organic osmolytes by chronic diuresis. Intra- and extracellular electrolyte concentrations at the papillary tip and the tissue contents of methylamines (glycerophosphorylcholine, betaine), polyols (myo-inositol, sorbitol), and several amino acids were determined in the different kidney zones by electron microprobe analysis and high-performance liquid chromatography in control animals, in rats infused for 6 days with furosemide via osmotic minipumps, and in rats given the vasopressin analogue [deamino-Cys1,D-Arg8]vasopressin (DDAVP) after the chronic furosemide treatment. Chronic diuresis greatly reduced interstitial tonicity and inner medullary contents of methylamines and polyols and moderately reduced inner medullary amino acid contents but did not significantly affect intracellular electrolyte concentrations. When the diuretic rats were infused with DDAVP for 2 h, interstitial tonicity more than doubled and intracellular K and Cl concentrations rose by approximately 60 and 160%, while inner medullary contents of methylamines, polyols, and amino acids were not changed significantly. These data demonstrate that after effective depletion of medullary organic osmolytes by long-term diuresis, the cells of the renal papilla adapt osmotically to an abrupt increase in extracellular tonicities by elevated cell electrolyte concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

PubMed1992

Effect of increased distal sodium delivery on organic osmolytes and cell electrolytes in the renal outer medulla.

Sodium absorption in distal tubule segments was stimulated by increasing the distal delivery via infusion of hypertonic saline. In these animals, and in control rats, electrolyte concentrations in thick ascending limb cells, light and dark cells of the collecting duct in the outer and inner stripe of the outer medulla and in cells of the proximal straight tubule (outer stripe only) were studied. The measurements were performed by electron microprobe analysis of freeze-dried cryosections of the outer medulla. In addition, organic osmolytes (glycerophosphorylcholine, betaine and myo-inositol) were measured by high performance liquid chromatography in cortex and outer medulla. Augmented delivery of sodium chloride to the distal tubule was associated with increased sodium concentrations of thick ascending limb cells both in the outer and inner stripe and of medullary collecting duct light and dark cells in the outer stripe. While the sum of organic osmolyte concentrations was 28% higher in the outer medulla of the salt-loaded animals compared with controls, this value was unchanged in the renal cortex. These findings indicate that the primary event underlying stimulation of sodium absorption along the thick ascending limb during increased distal sodium delivery is enhanced entry of sodium across the apical cell membrane. This would be expected to lead to higher cell sodium concentrations and stimulation of basolateral active Na-K-exchange. The enhanced transport activity of outer medullary tubules may be associated with increased interstitial tonicities and intracellular retention of organic osmolytes.

Animals↗

PubMed1992

Effect of K depletion on renal K and Rb excretion: evidence for activation of K reabsorption.

Prolonged potassium depletion activates tubular transport mechanisms mediating potassium absorption. To study ion specificity and factors that modulate the activity of potassium transport pathways, fractional potassium excretion (FEK) was compared with that of rubidium (FERb) in control and potassium-depleted rats subjected to various experimental maneuvers. In control rats FEK considerably surpassed FERb (FEK/FERb 1.54 +/- 0.08; mean +/- SEM), whereas in potassium-depleted rats FEK was significantly lower than FERb (FEK/FERb 0.72 +/- 0.05). Preferential retention of potassium compared to rubidium in potassium-depleted rats was accentuated (FEK/FERb 0.33 +/- 0.01) when residual potassium secretion was inhibited by amiloride and K-H exchange stimulated by increased distal buffer delivery (metabolic alkalosis). When distal fluid and buffer delivery were increased in control animals by acetazolamide, FEK and FERb rose in parallel. In potassium-depleted rats only FERb but not FEK was enhanced by acetazolamide. These data demonstrate that both potassium secretory and potassium absorptive transport pathways prefer potassium to its congener rubidium. Prolonged potassium depletion activates a potassium absorptive mechanism which is stimulated by increased distal buffer delivery and which transports potassium more effectively than rubidium.

Absorption↗

PubMed1992

Effect of loop diuretics on organic osmolytes and cell electrolytes in the renal outer medulla.

Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral Na-K-ATPase activity. In addition, the organic osmolytes glycerophosphorylcholine (GPC), betaine, inositol and sorbitol in cortex, outer medulla and inner medulla were measured using HPLC. Both loop diuretics significantly reduced sodium and chloride concentrations and rubidium uptake in thick ascending limb cells, but did not affect sodium concentration or rubidium uptake in the proximal straight tubule (PST) cells or in the light or dark cells of the outer medullary collecting duct (OMCD). Chloride concentrations in these cells (that is, PST cells, OMCD light and dark cells) were lowered by loop diuretics, albeit less than in thick ascending limb cells. Administration of both loop diuretics for only 20 minutes was sufficient to significantly depress tissue concentrations of GPC, betaine, and myo-inositol in the outer medulla and of GPC, betaine and sorbitol at the papillary tip. These results indicate that loop diuretics, presumably by blocking apical sodium entry, decrease thick ascending limb cellular sodium concentration and, as a consequence, reduce Na-K-ATPase activity as assessed by cell rubidium uptake. Although this has been shown previously in in vitro preparations, the present study confirms this for the first time in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Osmolytes.

The cells of the renal medulla osmotically adapt to chronic alterations in extracellular tonicity by appropriate changes in the intracellular contents of organic osmoeffectors. The major organic osmolytes are glycerophosphorylcholine, betaine, myo-inositol, sorbitol, and, possibly, taurine. When the concentrations of poorly permeant external solutes are acutely reduced, cells that have been adapted to high tonicities rapidly release organic osmolytes via specific transmembrane transport pathways. In contrast, when medullary cells are depleted of organic osmolytes, osmolyte accumulation on acute elevation of external tonicity is slow and involves stimulation of uptake, intracellular de novo synthesis, or inhibition of intracellular degradation, and is preceded by increased intracellular electrolyte concentrations. The available evidence suggests that this rise in intracellular ionic strength plays an important role in the initiation of those processes responsible for full adaptation of renal medullary cells to high tonicities. Recently, complementary DNAs encoding a myo-inositol and a betaine transporter have been isolated.

Animals↗

PubMed1992

Osmolytes in renal medulla during rapid changes in papillary tonicity.

The effect of acute changes in extracellular tonicity on cell electrolyte concentrations at the renal papillary tip and on organic osmolytes in different kidney zones was studied using electron microprobe analysis and high-performance liquid chromatography in four groups of rats: controls, 1- or 4-h water diuresis, and 4-h water diuresis followed by 30-min deamino-[Cys1,D-Arg8]vasopressin (ddAVP). The sum of the papillary interstitial concentrations of Na, K, and Cl was reduced from 981 mmol/kg wet wt in controls to 318 mmol/kg wet wt after 4-h diuresis and increased after ddAVP to 840 mmol/kg wet wt. In papillary collecting ducts intracellular electrolytes fell from 225 to 156 mmol/kg wet wt after 4-h diuresis and rose to 268 mmol/kg wet wt (significantly higher than control) after ddAVP. Organic osmolytes [sum of glycerophosphorylcholine (GPC), betaine, myo-inositol, and sorbitol] at the papillary tip decreased from 2,018 (control) to 1,037 mmol/kg protein after 4-h diuresis and did not increase after ddAVP. After ddAVP, cell P concentration, an index of cell GPC concentration, increased, indicating cell shrinkage. GPC concentration increased, indicating cell shrinkage. The results suggest that the concentrations of all osmoeffectors in papillary cells initially increase due to cell shrinkage in response to hypertonic stress. The higher intracellular ionic strength may be a signal for modulation of transport and metabolism of organic osmolytes.

Animals↗

PubMed1990

Regulation and localization of organic osmolytes in mammalian kidney.

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.

Animals↗