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C Hallbrucker

Publications and source records attributed to C Hallbrucker.

At least 19 recordsLinked to original sources
PubMed1994

Effects of urea on K+ fluxes and cell volume in perfused rat liver.

Exposure of the perfused rat liver to a perfusate made hyperosmotic by the presence of 200 mmol l-1 glucose led, as expected, to marked, transient hepatocellular shrinkage followed by volume-regulatory net K+ uptake. However, even after this volume-regulatory K+ uptake had ceased, the liver cells are still slightly shrunken. Withdrawal of glucose from the perfusate resulted in marked transient cell swelling, net K+ release from the liver and restoration of cell volume. However, when the Krebs-Henseleit perfusate was made hyperosmotic by the presence of urea (20-300 mM), there was no immediate decrease in liver mass, yet a slight and persistent cell shrinkage developing 2 min after the onset of exposure to urea. Surprisingly, urea induced concentration-dependent net K+ efflux from the liver and removal of urea net K+ reuptake from the inflowing perfusate. The urea (200 mM)-induced net K+ release resembled that observed following a lowering of the influent [NaCl]: making the perfusate hypoosmotic (245 mosmol l-1, by reducing influent [NaCl] by 30 mM) gave roughly the same K+ response as hyperosmotic exposure (505 mosmol/l) resulting from the presence of 200 mM urea. The urea-induced K+ efflux was not inhibited in the presence of ouabain (1 mM), or in Ca(++)-free perfusion, but was modified in the presence of quinidine (1 mM) or Ba++ (1 mM). The direction in which the liver was perfused had no effect on the urea-induced net K+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.

An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Häussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane.

Animals↗
PubMed1993

Hydroperoxide metabolism in rat liver. K+ channel activation, cell volume changes and eicosanoid formation.

Addition of t-butylhydroperoxide (0.2 mM) to isolated perfused rat liver led to a net K+ release of 7.2 +/- 0.2 mumol/g within 8 min and a net K+ reuptake of 6.6 +/- 0.4 mumol/g following withdrawal of the hydroperoxide, in line with earlier findings by Sies et al. [Sies, H., Gerstenecker, C., Summer, K. H., Menzel, H. & Flohé, R. (1974) in Glutathione (Flohé, L., Benöhr, C., Sies, H., Waller, H. D., eds) pp. 261-276, G. Thieme Publ. Stuttgart]. Net K+ release roughly paralleled the amount of GSSG released from the liver under the influence of the hydroperoxide. The t-butylhydroperoxide-induced K+ efflux was inhibited by approximately 70% in the presence of Ba2+ (1 mM), by 30% in Ca(2+)-free perfusions and was decreased by 50-60% when the intracellular Ca2+ stores were simultaneously depleted by repeated additions of phenylephrine. t-Butylhydroperoxide-induced K+ efflux was accompanied by a decrease of the intracellular water space by 58 +/- 14 microliter/g (n = 4), corresponding to a 10% cell shrinkage. The effect of t-butylhydroperoxide on cell volume was inhibited by 70-80% in the presence of Ba2+. In isolated rat hepatocytes treatment with t-butylhydroperoxide led to a slight hyperpolarization of the membrane at concentrations of 100 nM, but marked hyperpolarization occurred at t-butylhydroperoxide concentrations above 10 microM. t-Butylhydroperoxide (0.2 mM) transiently increased the portal-perfusion pressure by 3.3 +/- 0.6 cm H2O (n = 18), due to a slight stimulation of prostaglandin-D2 release under the influence of the hydroperoxide. In the presence of Ba2+ (1 mM), t-butylhydroperoxide increased the perfusion pressure by 12.7 +/- 1.2 cm H2O (n = 9) and produced an approximately tenfold increase of prostaglandin-D2 and thromboxane-B2 release. Under these conditions, glucose output from the liver rose from 0.9 +/- 0.03 to 2.9 +/- 0.7 mumol.g-1.min-1 (n = 4) with a time course roughly resembling that of portal-pressure increase and prostaglandin-D2 overflow. These effects were largely abolished in the presence of ibuprofen or the thromboxane-receptor-antagonist BM 13.177. The t-butylhydroperoxide effects on perfusion pressure, glucose and eicosanoid output were also enhanced in the presence of insulin or during hypotonic exposure; i.e. conditions known to swell hepatocytes, but not during hyperosmotic exposure. The data suggest that t-butylhydroperoxide induces liver-cell shrinkage and hyperpolarization of the plasma membrane due to activation of Ba(2+)-sensitive K+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Structural reaction pattern of hepatocytes following exposure to hypotonicity.

Isolated rat hepatocytes were exposed to hypotonic media (225 mosmol/l) for 5 and 15 min and processed for a quantitative electron microscopic stereologic analysis. Within 5 min of hypotonicity, the hepatocyte volume increased by 25% and thereafter displayed a volume regulatory decrease leading to mean cellular volume, which was 16% above that of controls. Stereologic analysis of the major subcellular compartment, the cytosol, showed an identical change as the whole cell. In contrast to that, the mitochondrial compartment increased in volume by 30% within the first 5 min of exposure and returned by regulatory volume decrease back to values of the isotonic controls after 15 min of hypotonicity. In contrast, hypotonicity (220 mosmol/l)-induced stimulation of flux through mitochondrial glutaminase and the glycine cleavage enzyme complex, as assessed by 14CO2 production from [1-14C]glutamine or [1-14C]glycine in isolated perfused rat liver persisted throughout a 15-min period of hypotonic exposure. Thus hypotonicity-induced alterations of mitochondrial metabolism apparently do not parallel the time course of mitochondrial volume changes. This suggests that persistent mitochondrial swelling is not required for functional alterations, but that the latter may be triggered by the initial swelling of mitochondria. Hypotonic exposure did not alter the nuclear volume of isolated hepatocytes. Cell membrane surface nearly doubled after 5 min of hypotonic exposure, but returned within 15 min of exposure to values observed in normotonic media. This may reflect the participation of exocytosis in hepatocyte volume regulation.

Animals↗
PubMed1992

Cell volume and bile acid excretion.

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.

Amino Acids↗
PubMed1992

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

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.

Amino Acids↗
PubMed1991

Regulation of cell volume in the perfused rat liver by hormones.

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.

Adenosine↗
PubMed1991

Increase of beta-actin mRNA upon hypotonic perfusion of perfused rat liver.

beta-Actin mRNA levels in livers exposed to hypotonic perfusion (from 305 to 225 mosmol/l) for one hour are increased 2-fold relative to albumin mRNA. Like albumin, glyceraldehyde-3-phosphate dehydrogenase and tyrosine aminotransferase mRNAs remain at the levels observed under normotonic conditions. The increase in beta-actin mRNA is interpreted as a cytoskeletal response due to cell swelling.

Actins↗
PubMed1991

Regulation of liver cell volume and proteolysis by glucagon and insulin.

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.

Animals↗
PubMed1991

Inhibition of hepatic proteolysis by insulin. Role of hormone-induced alterations of the cellular K+ balance.

1. Proteolysis was measured as [3H]leucine release from isolated perfused livers from rats, which had been labeled in vivo by an intraperitoneal injection of [3H]leucine about 16 h prior to the perfusion experiment. In livers from fed rats, insulin (35 nM) inhibited [3H]leucine release by 24.5 +/- 1.3% (n = 15) and led to an amiloride-sensitive, bumetanide-sensitive and furosemide-sensitive net K+ uptake of 5.53 +/- 0.31 mumol.g-1 (n = 15). Both the insulin effects on net K+ uptake and on [3H]leucine release were diminished by about 65% or 55% in presence of furosemide (0.1 mM) or bumetanide (5 microM), respectively. The insulin-induced net K+ uptake was virtually abolished in the presence of amiloride (1 mM) plus furosemide (0.1 mM). 2. In perfused livers from 24-h-starved rats, both the insulin-stimulated net K+ uptake and the insulin-induced inhibition of [3H]leucine release were about 80% lower than observed in experiments with livers from fed rats. The insulin effects on K+ balance and [3H]leucine release were not significantly influenced in the presence of glycine (2 mM), although glycine itself inhibited [3H]leucine release by 30.3 +/- 0.3% (n = 4) and 13.8 +/- 1.2% (n = 5) in livers from starved and fed rats, respectively. When livers from fed rats were preswollen by hypoosmotic perfusion (225 mOsmol.l-1), both the insulin-induced net K+ uptake and the inhibition of [3H]leucine release were diminished by 50-60%. 3. During inhibition of [3H]leucine release by insulin, further addition of glucagon (100 nM) led to a marked net K+ release from the liver (3.82 +/- 0.24 mumol.g-1), which was accompanied by stimulation of [3H]leucine release by 16.4 +/- 4.6% (n = 4). 4. Ba2+ (1 mM) infusion led to a net K+ uptake by the liver of 3.2 +/- 0.2 mumol.g-1 (n = 4) and simultaneously inhibited [3H]leucine release by 12.4 +/- 1.7% (n = 4). 5. There was a close relationship between the Ba2+ or insulin-induced net K+ uptake and the degree of inhibition of [3H]leucine release, even when the K+ response to insulin was modulated by bumetanide, furosemide, glucagon, hypotonic or glycine-induced cell swelling or the nutritional state. 6. The data suggest that the insulin-induced net K+ uptake involves activation of both NaCl/KCl cotransport and Na+/H+ exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1991

Role of eicosanoids, inositol phosphates and extracellular Ca2+ in cell-volume regulation of rat liver.

1. In isolated perfused rat liver, the time-course of volume-regulatory K+ efflux following exposure to hypoosmolar perfusate resembled the leukotriene-C4-induced K+ efflux in normotonic perfusion. Omission of Ca2+ from the perfusion fluid had no effect on volume-regulatory K+ efflux, but abolished completely the leukotriene-C4-induced K+ efflux. 2. Volume-regulatory K+ fluxes following hypoosmolar exposure (225 mOsmol l-1) and subsequent reexposure to normotonic media (305 mOsmol l-1) were not significantly affected by the cyclooxygenase inhibitors indomethacin (5 mumol l-1) or ibuprofen (50 mumol l-1), the leukotriene D4/C4-receptor antagonist 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl]etha none (YL 171883, 50 microM), the lipoxygenase inhibitor nordihydroguaiaretic acid (20 microM), the phospholipase-A2 inhibitor bromophenacyl bromide (50 microM) or the thromboxane-receptor antagonist 4-[2-(benzenesulfonamido)ethyl]-phenoxyacetic acid (BM 13.177, 20 microM). Also the effects of hypoosmotic cell swelling on lactate, pyruvate and glucose balance across the liver remained largely unaffected in presence of these inhibitors. Neither exposure of perfused rat liver to hypoosmolar (225 mOsmol l-1) nor to hyperosmolar (385 mOsmol l-1) perfusion media affected hepatic prostaglandin-D2 release. 3. When livers were 3H-labeled in vivo by an intraperitoneal injection of myo-[2-3H]inositol about 16 h prior to the perfusion experiment, cell swelling due to lowering the perfusate osmolarity from 305 mOsmol l-1 to 225 mOsmol l-1 led to about a threefold stimulation of [3H]inositol release. The maximum of hypotonicity-induced [3H]inositol release preceded maximal volume-regulatory K+ efflux by about 30 s, but came after the maximum of water shift into the cells. Hypotonicity-induced [3H]inositol release was largely prevented in presence of Li+ (10 mM), but simultaneously inositol monophosphate accumulated inside the liver within 10 min and a small, but significant increase of inositol trisphosphate 1 min after onset of hypoosmolar exposure was detectable. No stimulation of [3H]inositol release was observed during cell shrinkage by switching the perfusate osmolarity from 225 mOsmol l-1 to 305 mOsmol l-1 or from 305 mOsmol l-1 to 385 mOsmol l-1. No stimulation of [3H]inositol release was observed upon swelling of preshrunken livers by lowering the osmolarity from 385 mOsmol l-1 to 305 mOsmol l-1, although the volume-regulatory K+ efflux under these conditions was almost identical to that observed after lowering the osmolarity from 305 mOsmol l-1 to 225 mOsmol l-1. 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Cell volume is a major determinant of proteolysis control in liver.

Hepatic proteolysis is inhibited by insulin, amino acids and hypoosmotic cell swelling and is stimulated by glucagon. These effectors simultaneously modulate cell volume in the intact liver, as shown by measurements of the intracellular water space. A close relationship exists between the effect on proteolysis and the accompanying cell volume change, regardless of whether hepatic proteolysis was modified by insulin, glucagon, cyclic AMP, glutamine, glycine, barium of hypoosmotic exposure. It is suggested that cell volume changes exerted by hormones and amino acids play a crucial role in the regulation of hepatic proteolysis.

Animals↗
PubMed1991

Control of hepatic proteolysis by amino acids. The role of cell volume.

1. Proteolysis in isolated perfused rat liver was monitored as [3H]leucine release into effluent perfusate after in vivo labeling by intraperitoneal injection of [3H]leucine about 16 h prior to the perfusion experiment. Exposure of the livers to hypotonic perfusion media (175-295 mOsmol.l-1) increased liver mass due to cell swelling and inhibited [3H]leucine release. The extent of inhibition of [3H]leucine release was linearly related to the liver-mass increase, regardless of whether livers from fed or 24-h-starved rats were studied. 2. Infusion of glycine (0.5-3 mmol.l-1) or glutamine (0.5-3 mmol.l-1) during normotonic perfusions (305 mOsmol.l-1) led to a concentration-dependent increase of liver mass and inhibition of [3H]leucine release. The inhibition of [3H]leucine release was again strongly dependent upon the increase of liver mass, regardless of whether cell swelling was induced by glutamine or glycine in normotonic perfusions, by exposure of the liver to hypotonic media or whether amino-acid-induced cell swelling was modified by the nutritional state. The effects of glutamine and glycine on [3H]leucine release were additive to the same extent as that found when the liver-mass increase was observed. 3. Alanine, serine and proline inhibited [3H]leucine release in parallel to the extent of amino-acid-induced liver-mass increase; however, the inhibition of [3H]leucine release was about twice that found when comparable degrees of cell swelling were induced either by hypotonic exposure or by addition of glutamine or glycine. The relationship between alanine-induced liver-mass increase and the inhibition of [3H]leucine release was also maintained in presence of aminooxyacetate (0.2 mmol.l-1). 4. Infusion of an amino acid mixture, roughly mimicking the concentrations found in portal venous blood, to livers from 24-h-starved or fed rats inhibited [3H]leucine release by 56.0 +/- 2.4% (n = 6) or 31.1 +/- 2.3% (n = 3), respectively, and increased liver mass by 5.0 +/- 0.1% (n = 6) or 2.2 +/- 0.3% (n = 3), respectively. Regardless of the nutritional state, there was a close relationship between the amino-acid-mixture-induced (and also phenylalanine-induced) increase of liver mass and the degree of inhibition of [3H]leucine release; however, the inhibition of [3H]leucine release was about fourfold higher than that found when comparable degrees of cell swelling were induced by hypotonic exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1991

Modification of liver cell volume by insulin and glucagon.

Cell volume plays a decisive role in the regulation of hepatic metabolism. The present study has been performed to test for an effect of insulin and glucagon on liver cell volume. To this end, the effect of these hormones has been studied in isolated perfused rat livers and isolated rat hepatocytes. Insulin leads to rapid stimulation of cellular K+ uptake and increase of cell volume, effects reversed by glucagon or cAMP. The insulin stimulated cellular K+ uptake is significantly decreased in the presence of either loop diuretics (furosemide or bumetanide) or amiloride and is completely inhibited in the presence of both, bumetanide and amiloride. The glucagon stimulated cellular K+ release in the presence of insulin is blunted by K+ channel blocker quinidine. The effects of insulin and glucagon on liver cell volume could participate in the regulation of hepatic metabolism by these hormones.

Animals↗
PubMed1991

Hepatorenal reflex regulating kidney function.

In anesthetized male rats, infusion of glutamine (2 mumol/min) into the superior mesenteric vein at a rate known to induce liver cell swelling leads to marked decreases in renal glomerular filtration rate, renal para-aminohippurate clearance and urinary flow rate. Glutamine infused at identical rates into the jugular vein does not elicit any of these effects. The effect of glutamine is mimicked by serine but not by glutamate. Spinal transection, renal denervation or section of the vagal hepatic nerves abolishes the effect of mesenteric venous glutamine infusion. Mesenteric application of glucagon (1 ng/min) or of both glutamine and glucagon enhances glomerular filtration rate and urinary flow rate. Infusion of 1 ng/min glucagon through the jugular vein does not significantly alter glomerular filtration rate or urinary flow rate. The data disclose a powerful liver-borne mechanism regulating kidney function that is mediated by the hepatorenal innervation.

Animals↗
PubMed1991

A non-invasive technique for cell volume determination in perfused rat liver.

1) In isolated perfused rat liver, the intracellular ([14C]urea-accessible minus [3H]inulin accessible) water space was determined from the washout profiles of simultaneously infused [3H]inulin and [14C]urea. The washout profile of infused [14C]urea was indistinguishable from that of infused tritiated water. During normotonic perfusions and without hormones or amino acids in influent, the intracellular water space was 548 +/- 10 microliters/g liver wet weight (n = 44). Use of [3H]raffinose instead of [3H]inulin as marker for the extracellular space yielded almost identical values for the intracellular water space (i.e. 98.9 +/- 0.2% of that found with [3H]inulin/[14C]urea). When volume-regulatory K+ fluxes were completed following hypo- and hypertonic exposure of perfused rat livers and a steady state was reached, the intracellular water space was found to be increased and decreased, respectively. The extent of anisotonic exposure was linearly related to the change of intracellular water space. 2) Anisotonicity-, glutamine- and glycine-induced liver mass changes were almost fully explained by the simultaneously occurring alterations of the intracellular water space, indicating that cell volume changes in perfused rat liver under these conditions are not accompanied by significant changes of the extracellular space. Volume-regulatory K+ (plus accompanying anion) efflux following hypotonic perfusion accounted for about 70-85% of regulatory cell volume decrease, which occurred during the first 10 min of hypotonic exposure. 3) Cell volume of isolated hepatocytes was determined as the "hepatocrit" after gentle centrifugation of the cell suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cell swelling inhibits proteolysis in perfused rat liver.

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.

Animals↗