scholarly journals Cell volume and bile acid excretion

1992 ◽  
Vol 288 (2) ◽  
pp. 681-689 ◽  
Author(s):  
D Häussinger ◽  
C Hallbrucker ◽  
N Saha ◽  
F Lang ◽  
W Gerok
Keyword(s):  
Amino Acids ◽  
Cell Volume ◽  
Liver Cell ◽  
Bile Flow ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Cell Shrinkage ◽  
Volume Changes ◽  
Close Relationship ◽  
Stimulation Of

The interaction between cell volume and taurocholate excretion into bile was studied in isolated perfused rat liver. Cell swelling due to hypo-osmotic exposure, addition of amino acids or insulin stimulated taurocholate excretion into bile and bile flow, whereas hyperosmotic cell shrinkage inhibited these. These effects were explained by changes in Vmax of taurocholate excretion into bile: Vmax. increased from about 300 to 700 nmol/min per g after cell swelling by 12-15% caused by either hypo-osmotic exposure or addition of amino acids under normo-osmotic conditions. Steady-state taurocholate excretion into bile was not affected when the influent K+ concentration was increased from 6 to 46 mM or decreased to 1 mM with iso-osmoticity being maintained by corresponding changes in the influent Na+ concentration. Replacement of 40 mM-NaCl by 80 mM-sucrose decreased taurocholate excretion into bile by about 70%; subsequent hypo-osmotic exposure by omission of sucrose increased taurocholate excretion to 160%. Only minor, statistically insignificant, effects of aniso-osmotic cell volume changes on the appearance of bolus-injected horseradish peroxidase in bile were observed. Taurocholate (400 microM) exhibited a cholestatic effect during hyperosmotic cell shrinkage, but not during hypo-osmotic cell swelling. Both taurocholate and tauroursodeoxycholate increased liver cell volume. Tauroursodeoxycholate stimulated taurocholate (100 microM) excretion into bile. This stimulatory effect was strongly dependent on the extent of tauroursodeoxycholate-induced cell swelling. During continuous infusion of taurocholate (100 microM) further addition of tauroursodeoxycholate at concentrations of 20, 50 and 100 microM increased cell volume by 10, 8 and 2% respectively, in parallel with a stimulation of taurocholate excretion into bile by 29, 27 and 9% respectively. There was a close relationship between the extent of cell volume changes and taurocholate excretion into bile, regardless of whether cell volume was modified by tauroursodeoxycholate, amino acids or aniso-osmotic exposure. The data suggest that: (i) liver cell volume is one important factor determining bile flow and biliary taurocholate excretion; (ii) swelling-induced stimulation of taurocholate excretion into bile is probably not explained by alterations of the membrane potential; (iii) bile acids modulate liver cell volume; (iv) taurocholate-induced cholestasis may depend on cell volume; (v) stimulation of taurocholate excretion into bile by tauroursodeoxycholate can largely be explained by tauroursodeoxycholate-induced cell swelling.

scholarly journals Cell swelling increases bile flow and taurocholate excretion into bile in isolated perfused rat liver

1992 ◽  
Vol 281 (3) ◽  
pp. 593-595 ◽  
Author(s):  
C Hallbrucker ◽  
F Lang ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Cell Volume ◽  
Rat Liver ◽  
Bile Flow ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Volume Changes ◽  
Close Relationship

The effects of aniso-osmotically and amino-acid-induced cell-volume changes on bile flow and biliary taurocholate excretion were studied in isolated perfused rat liver. With taurocholate (100 microM) in the influent perfusate, hypo-osmotic exposure (225 mosmol/l) increased taurocholate excretion into bile and bile flow by 42 and 27% respectively, whereas inhibition by 32 and 47% respectively was observed after hyperosmotic (385 mosmol/l) exposure. The effects of aniso-moticity on taurocholate excretion into bile was observed throughout aniso-osmotic exposure, even after completion of volume-regulatory ion fluxes and were fully reversible upon re-exposure to normo-osmotic media. Hypo-osmotic cell swelling (225 mosmol/l) increased the Vmax. of taurocholate translocation from the sinusoidal compartment into bile about 2-fold. Also, cell swelling induced by glutamine and glycine stimulated both bile flow and biliary taurocholate excretion. There was a close relationship between the aniso-osmotically and amino-acid-induced change of cell volume and taurocholate excretion into bile. The data suggest that liver cell volume plays an important role in regulating bile-acid-dependent bile flow and biliary taurocholate excretion.

scholarly journals Regulation of liver cell volume and proteolysis by glucagon and insulin

1991 ◽  
Vol 278 (3) ◽  
pp. 771-777 ◽  
Author(s):  
S Vom Dahl ◽  
C Hallbrucker ◽  
F Lang ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Cell Volume ◽  
Liver Cell ◽  
Intracellular Water ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Cell Shrinkage ◽  
Glucagon And Insulin ◽  
Opposing Effects ◽  
Water Space

The effects of insulin and glucagon on liver cell volume and proteolysis were studied in isolated perfused rat liver. The rate of proteolysis was assessed as [3H]leucine release from single-pass-perfused livers from rats which had been prelabelled in vivo by intraperitoneal injection of [3H]leucine. The intracellular water space was determined from the wash-out profiles of simultaneously added [3H]inulin and [14C]urea. In normo-osmotic (305 mosM) control perfusions the intracellular water space was 548 +/- 10 microliters/g wet mass (n = 44) and was increased by 16.5 +/- 2.6% (n = 6), i.e. by 85 +/- 14 microliters/g, after hypoosmotic exposure (225 mosM). Glucagon (0.1 microM) decreased the intracellular water space by 17 +/- 4% (n = 4), whereas insulin (35 nM) increased the intracellular water space by 9.3 +/- 1.4% (n = 15). Also, in isolated rat hepatocyte suspensions insulin (100 nM) caused cell swelling by 10.7 +/- 1.8% (n = 16), which was fully reversed by glucagon. In perfused liver, insulin-induced cell swelling was accompanied by a hepatic net K+ uptake (4.5 +/- 0.2 mumol/g) and an inhibition of proteolysis by 21 +/- 2% (n = 12); further addition of glucagon led to a net K+ release of 3.8 +/- 0.2 mumol/g (n = 7) and fully reversed the insulin effects on both cell volume and proteolysis. Similarly, insulin-induced cell swelling and inhibition of proteolysis were completely antagonized by hyperosmotic (385 mosM) cell shrinkage. Furthermore, cell swelling and inhibition of proteolysis after hypo-osmotic exposure or amino acid addition were reversed by glucagon-induced cell shrinkage. There was a close relationship between the extent of cell swelling and the inhibition of proteolysis, regardless of whether cell volume was modified by insulin, glucagon or aniso-osmotic exposure. The data show that glucagon and insulin are potent modulators of liver cell volume, at least in part by alterations of cellular K+ balance, and that their opposing effects on hepatic proteolysis can largely be explained by opposing effects on cell volume. It is hypothesized that hormone-induced alterations of cell volume may represent an important, not yet recognized, mechanism mediating hormonal effects on metabolism.

scholarly journals Regulation of cell volume in the perfused rat liver by hormones

1991 ◽  
Vol 280 (1) ◽  
pp. 105-109 ◽  
Author(s):  
S vom Dahl ◽  
C Hallbrucker ◽  
F Lang ◽  
D Häussinger
Keyword(s):  
Cell Volume ◽  
Rat Liver ◽  
Liver Cell ◽  
Intracellular Water ◽  
Cell Swelling ◽  
Perfused Rat Liver ◽  
Hormone Action ◽  
Cell Shrinkage ◽  
Volume Changes ◽  
Water Space

The effect of hormones on cell volume was studied in isolated perfused rat liver by assessing the intracellular water space as the difference between a [3H]inulin- and a [14C]urea-accessible space. The intracellular water space (control value 559 +/- 7 microliters/g of liver; n = 88) increased on addition of insulin (35 nM) or phenylephrine (5 microM) by 12 or 8% respectively, whereas it decreased with cyclic AMP (cAMP; 50 microM), glucagon (100 nM) or adenosine (50 microM) by 9, 13 or 6% respectively. Both insulin and glucagon exerted half-maximal effects on cell volume and cellular K+ balance at hormone concentrations found physiologically in the portal vein. Adenosine-induced cell shrinkage was explained by a net K+ release from the liver. Phenylephrine (5 microM) led to cell swelling by about 8%, which was additive to insulin-induced swelling. Extracellular ATP (20 microM) induced cell shrinkage by about 6%; this was additive to adenosine-induced shrinkage. Vasopressin (15 nM) did not appreciably change cell volume, but induced marked cell shrinkage when glucagon or cAMP was present. Insulin- and phenylephrine-induced cell swelling was counteracted by cAMP. Hormone-induced changes of intracellular water space could sufficiently explain accompanying liver mass changes induced by glucagon, cAMP, adenosine or vasopressin, but not those by phenylephrine and extracellular ATP. The data show that liver cell volume is subject to hormonal regulation, in part owing to modification of cellular K+ balance. Glucagon- and insulin-induced cell volume changes occur already in the presence of physiological hormone concentrations. The effects of Ca2(+)-mobilizing hormones on cell volume are not uniform. In view of the recently established role of cell volume changes in modulating liver cell function, the present findings open a new perspective on the mechanisms of hormone action in liver, underlining our previous hypothesis that cell volume changes may represent a ‘second messenger’ of hormone action.

Agonist-induced cytoplasmic volume changes in cultured rabbit parietal cells

2000 ◽  
Vol 279 (1) ◽  
pp. G40-G48 ◽  
Author(s):  
Thorsten Sonnentag ◽  
Wolf-Kristian Siegel ◽  
Oliver Bachmann ◽  
Heidi Rossmann ◽  
Andreas Mack ◽  
...  
Keyword(s):  
Volume Regulation ◽  
Parietal Cells ◽  
Cell Swelling ◽  
Secretory Process ◽  
Cell Shrinkage ◽  
Rapid Loss ◽  
Volume Changes ◽  
Volume Increase ◽  
Regulatory Volume Increase ◽  
Stimulation Of

Concomitant Na+/H+ and Cl−/HCO3 − exchange activation occurs during stimulation of acid secretion in cultured rabbit parietal cells, possibly related to a necessity for volume regulation during the secretory process. We investigated whether cytoplasmic volume changes occur during secretagogue stimulation of cultured rabbit parietal cells. Cells were loaded with the fluorescent dye calcein, and the calcein concentration within a defined cytoplasmic volume was recorded by confocal microscopy. Forskolin at 10−5 M, carbachol at 10−4 M, and hyperosmolarity (400 mosmol) resulted in a rapid increase in the cytoplasmic dye concentration by 21 ± 6, 9 ± 4, and 23 ± 5%, respectively, indicative of cell shrinkage, followed by recovery to baseline within several minutes, indicative of regulatory volume increase (RVI). Depolarization by 5 mM barium resulted in a decrease of the cytoplasmic dye concentration by 10 ± 2%, indicative of cell swelling, with recovery within 15 min, and completely prevented forskolin- or carbachol-induced cytoplasmic shrinkage. Na+/H+ exchange inhibitors slightly reduced the initial cell shrinkage and significantly slowed the RVI, whereas 100 μM bumetanide had no significant effect on either parameter. We conclude that acid secretagoguges induce a rapid loss of parietal cell cytoplasmic volume, followed by RVI, which is predominantly mediated by Na+/H+ and Cl−/HCO3 − exchange.

Effects of apical membrane Cl(-)-formate exchange on cell volume in rabbit proximal tubule

1990 ◽  
Vol 258 (3) ◽  
pp. F530-F536 ◽  
Author(s):  
L. Schild ◽  
P. S. Aronson ◽  
G. Giebisch
Keyword(s):  
Proximal Tubule ◽  
Cell Volume ◽  
Apical Membrane ◽  
Cell Swelling ◽  
Volume Changes ◽  
Proximal Tubule Cells ◽  
Volume Increase ◽  
Tubule Lumen ◽  
Stimulation Of

We used real-time recordings of cell volume changes to test for the role of the Cl(-)-formate exchanger in mediating NaCl entry across the apical membrane of rabbit proximal tubule cells. In the absence of extracellular Cl-, 0.5 and 5 mM formate in the tubule lumen induced an increase in cell volume of 1 and 9%, respectively. Formate-induced cell swelling was reduced by alkalinizing the tubule lumen or by addition of luminal amiloride (2 mM), indicating that the increase in cell volume results from the intracellular accumulation of Na-formate via nonionic diffusion of formic acid in parallel with Na(+)-H+ exchange. The cell volume increase induced by 0.5 mM formate was potentiated (from 1 to 4%) by Cl-, as expected for a formate-mediated stimulation of NaCl uptake via parallel Cl(-)-formate exchange and Na(+)-H+ exchange across the apical membrane. By contrast, the cell volume increase induced by 5 mM formate was attenuated (from 9 to 4%) by Cl-. The attenuating effect of Cl- on formate-induced cell swelling required the operation of the apical membrane Cl(-)-formate exchanger. The effect of 1:1 Cl(-)-formate exchange to attenuate formate-induced cell swelling can be explained if the cell possesses a volume-activated anion exit pathway, most likely at the basolateral cell membrane, that is capable of mediating the efflux of Cl- but not formate from the cell.

Physiology and pathophysiology of Na+/H+exchange and Na+-K+-2Cl−cotransport in the heart, brain, and blood

2006 ◽  
Vol 291 (1) ◽  
pp. R1-R25 ◽  
Author(s):  
S. F. Pedersen ◽  
M. E. O'Donnell ◽  
S. E. Anderson ◽  
P. M. Cala
Keyword(s):  
Cell Volume ◽  
Cell Function ◽  
Cell Damage ◽  
Cellular Responses ◽  
Exercise Stress ◽  
Cell Swelling ◽  
Cell Shrinkage ◽  
Comprehensive Overview ◽  
Wide Range ◽  
Stimulation Of

Maintenance of a stable cell volume and intracellular pH is critical for normal cell function. Arguably, two of the most important ion transporters involved in these processes are the Na+/H+exchanger isoform 1 (NHE1) and Na+-K+-2Cl−cotransporter isoform 1 (NKCC1). Both NHE1 and NKCC1 are stimulated by cell shrinkage and by numerous other stimuli, including a wide range of hormones and growth factors, and for NHE1, intracellular acidification. Both transporters can be important regulators of cell volume, yet their activity also, directly or indirectly, affects the intracellular concentrations of Na+, Ca2+, Cl−, K+, and H+. Conversely, when either transporter responds to a stimulus other than cell shrinkage and when the driving force is directed to promote Na+entry, one consequence may be cell swelling. Thus stimulation of NHE1 and/or NKCC1 by a deviation from homeostasis of a given parameter may regulate that parameter at the expense of compromising others, a coupling that may contribute to irreversible cell damage in a number of pathophysiological conditions. This review addresses the roles of NHE1 and NKCC1 in the cellular responses to physiological and pathophysiological stress. The aim is to provide a comprehensive overview of the mechanisms and consequences of stress-induced stimulation of these transporters with focus on the heart, brain, and blood. The physiological stressors reviewed are metabolic/exercise stress, osmotic stress, and mechanical stress, conditions in which NHE1 and NKCC1 play important physiological roles. With respect to pathophysiology, the focus is on ischemia and severe hypoxia where the roles of NHE1 and NKCC1 have been widely studied yet remain controversial and incompletely elucidated.

scholarly journals Cell swelling inhibits proteolysis in perfused rat liver

1990 ◽  
Vol 272 (1) ◽  
pp. 239-242 ◽  
Author(s):  
D Häussinger ◽  
C Hallbrucker ◽  
S vom Dahl ◽  
F Lang ◽  
W Gerok
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Liver Cell ◽  
Intraperitoneal Injection ◽  
Branched Chain Amino Acids ◽  
Cell Swelling ◽  
Perfused Rat Liver ◽  
Close Relationship ◽  
Branched Chain

Exposure of isolated single-pass-perfused rat liver to hypo-osmotic media resulted in liver cell swelling and an inhibition of release of branched-chain amino acids. Similarly, cell swelling inhibited [3H]leucine release from perfused livers from rats in which liver proteins were prelabelled in vivo by intraperitoneal injection of L-[4,5-3H]leucine 16-20 h before the experiment. The effects of cell swelling on [3H]leucine release were fully reversible. [3H]Leucine release was also inhibited when cell swelling was induced by addition of glutamine (0.5-2 mM). There was a close relationship between the inhibition of [3H]leucine release and the degree of liver cell swelling, regardless of whether cell swelling was induced by hypo-osmotic perfusion or addition of glutamine. The data suggest that the known anti-proteolytic effect of glutamine is in large part due to glutamine-induced hepatocyte swelling.

Liver cell hydration and integrin signaling

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Bonus ◽  
Dieter Häussinger ◽  
Holger Gohlke
Keyword(s):  
Cell Volume ◽  
Liver Cell ◽  
Cell Function ◽  
The Other ◽  
Signaling Cascades ◽  
Integrin Signaling ◽  
Volume Changes ◽  
The One ◽  
And Oxidative Stress

Abstract Liver cell hydration (cell volume) is dynamic and can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such volume changes were identified as a novel and important modulator of cell function. It provides an early example for the interaction between a physical parameter (cell volume) on the one hand and metabolism, transport, and gene expression on the other. Such events involve mechanotransduction (osmosensing) which triggers signaling cascades towards liver function (osmosignaling). This article reviews our own work on this topic with emphasis on the role of β1 integrins as (osmo-)mechanosensors in the liver, but also on their role in bile acid signaling.

Regulation of cell function by the cellular hydration state

1994 ◽  
Vol 267 (3) ◽  
pp. E343-E355 ◽  
Author(s):  
D. Haussinger ◽  
F. Lang ◽  
W. Gerok
Keyword(s):  
Cell Volume ◽  
Cell Function ◽  
Narrow Range ◽  
Cell Swelling ◽  
Metabolic Function ◽  
Cell Shrinkage ◽  
Short Term ◽  
Hydration State ◽  
Per Se ◽  
And Oxidative Stress

Cellular hydration can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such short-term modulation of cell volume within a narrow range acts per se as a potent signal which modifies cellular metabolism and gene expression. It appears that cell swelling and cell shrinkage lead to certain opposite patterns of cellular metabolic function. Apparently, hormones and amino acids can trigger those patterns simply by altering cell volume. Thus alterations of cellular hydration may represent another important mechanism for metabolic control and act as another second or third messenger linking cell function to hormonal and environmental alterations.

Volume-sensitive Ca influx and release from intracellular pools in gastric parietal cells

1992 ◽  
Vol 263 (3) ◽  
pp. C584-C589 ◽  
Author(s):  
P. A. Negulescu ◽  
B. Munck ◽  
T. E. Machen
Keyword(s):  
Image Processing ◽  
Cell Volume ◽  
Digital Image Processing ◽  
Parietal Cells ◽  
Cell Swelling ◽  
Cell Shrinkage ◽  
Gastric Glands ◽  
Intact Rabbit ◽  
Induced Changes ◽  
Gastric Parietal Cells

The effects of osmotically induced changes in cell volume on cytoplasmic free Ca (Cai) were studied in parietal cells from intact rabbit gastric glands using digital image processing of fura-2 fluorescence. In resting unstimulated cells, Cai was unaffected by either cell swelling or shrinking when osmolarity was varied between 200 and 400 mosM (isotonicity 290 mosM). However, when cells were swelled in a 165 mosM solution (55% tonicity), a biphasic Ca increased was observed. On average, Cai increased transiently from 80 to 218 nM before stabilizing at approximately 140 nM. The peak was due to release from intracellular pools because it was present in Ca-free solutions while the sustained elevation was dependent on external Ca. In carbachol-stimulated cells, Ca influx was most sensitive to cell shrinkage. For example, addition of 25 mM sucrose (108% tonicity) caused a 30% decrease in the sustained carbachol-stimulated Cai increase (plateau). In contrast, carbachol-stimulated cells were relatively insensitive to cell swelling, with a 30% decrease in tonicity causing only a 15% increase in the plateau. However, as in the unstimulated cells, extreme (55% tonicity) swelling caused additional increases in Cai levels. The carbachol-dependent effects of changes in cell volume on Cai could be mimicked by treating cells with thapsigargin, an inhibitor of Ca pumps of intracellular membranes that also has been shown to stimulate Ca entry. Thus, although extreme swelling conditions (55% tonicity) could elicit Cai increases in either the presence or absence of agonist, agonist was required to observe Cai decreases due to cell shrinkage.(ABSTRACT TRUNCATED AT 250 WORDS)

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