Cell-swelling-induced taurine release from isolated perfused rat liver

1994 ◽  
Vol 72 (1-2) ◽  
pp. 8-11 ◽  
Author(s):  
H. S. Brand ◽  
A. J. Meijer ◽  
L. A. Gustafson ◽  
G. G. A. Jörning ◽  
A. C. J. Leegwater ◽  
...  
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Liver Mass ◽  
Taurine Release ◽  
Perfusion Medium ◽  
Nacl Concentration ◽  
Isolated Liver

Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The osmolarity of the perfusion medium was reduced from 305 to 255 or 205 mosM by decreasing the NaCl concentration 25 or 50 mM, respectively. This induced an 6–8% increase in liver mass and was associated with a specific 1.7-fold (−50 mosM) and 14-fold (−100 mosM) increase of the taurine release. None of the other amino acids measured showed a significant increase in their concentration in the effluent. The increase in taurine release occurred within 30 s after exposure to hypotonicity (maximal after 1–1.5 min) and followed closely the changes in liver mass. The taurine release declined gradually during successive exposures of the isolated liver to −100 mosM. This release was 29 and 17% of the original during the second and third exposure, respectively.Key words: cell swelling, liver, taurine.

scholarly journals Metabolism of inorganic sulphate in the isolated perfused rat liver. Effect of sulphate concentration on the rate of sulphation by phenol sulphotransferase

1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Physiological Concentration ◽  
Sulphate Concentration ◽  
Inorganic Sulphate

1. The metabolism of inorganic [35S]sulphate (Na235SO4) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [35S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high Km of synthesis of adenosine 3′-phosphate 5′-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3′-phosphate 5′-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.

Removal of Excess Cholesterol and Cholate by the Isolated Rat Liver From its Perfusate

1956 ◽  
Vol 184 (2) ◽  
pp. 412-414 ◽  
Author(s):  
Meyer Friedman ◽  
René Bine ◽  
Tad Ishida
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Isolated Rat Liver ◽  
Almost All ◽  
Isolated Liver ◽  
Isolated Rat

Perfusion of the isolated perfused rat liver with a perfusate containing hypercholesteremic and hypercholatemic blood results in the removal of some of the cholesterol and almost all of the excess cholate. The withdrawn cholesterol is deposited almost completely in the liver, whereas the withdrawn cholate is excreted promptly in the bile. It is concluded that the isolated liver behaves qualitatively similar to the liver of the intact rat in respect to cholesterol and cholate metabolism.

scholarly journals Endogenous hydroperoxide formation, cell volume and cellular K+ balance in perfused rat liver

1993 ◽  
Vol 296 (3) ◽  
pp. 701-707 ◽  
Author(s):  
N Saha ◽  
R Schreiber ◽  
S vom Dahl ◽  
F Lang ◽  
W Gerok ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Liver Mass ◽  
Hydroperoxide Formation ◽  
Close Relationship ◽  
H2o2 Formation ◽  
Net Release ◽  
K Release

Addition of benzylamine (0.5 mM) to isolated perfused rat liver led to a net release of K+ of 10.5 +/- 0.3 mumol/g, which was accompanied by a decrease in liver mass by 9.3 +/- 0.4% and a decrease of the intracellular water space by 13.7 +/- 0.6%, suggestive of hepatocellular shrinkage. Benzylamine had no effect on the perfusion pressure, and there was a close relationship between benzylamine-induced net K+ release and the accompanying decrease in liver mass. Benzylamine-induced net K+ release was sensitive to inhibition of monoamine oxidase by pargyline and increased with benzylamine flux through monoamine oxidase, suggesting its dependence on intracellular H2O2 formation. In line with this, infusion of H2O2 (but not of benzaldehyde, the other product of benzylamine metabolism) stimulated net K+ release from the liver. However, at a given H2O2 load K+ release was about 2-3-fold higher when H2O2 was generated intracellularly during the oxidation of benzylamine, as compared with exogenously delivered H2O2. Inhibition of catalase by 3-amino-1,2,4-triazole (0.2 mM) significantly increased the benzylamine-induced net K+ release as well as the benzylamine-induced release of GSSG into bile, but had no effect on benzylamine oxidation at monoamine oxidase. In the presence of Ba2+ (1 mM) or in Ca(2+)-free perfusions, the benzylamine-induced net K+ efflux was diminished by 60-70% or about 30%, respectively. This was not explained by the 20-30% decrease in flux through monoamine oxidase observed under these conditions. The results suggest that metabolic generation of H2O2 inside the liver leads to a net K+ efflux and subsequent hepatocellular shrinkage. Net K+ efflux under these conditions is enhanced when catalase is inhibited, suggesting that the rate of both intracellular H2O2 generation and degradation can modulate cellular K+ balance and cellular volume. The data support the idea that oxidative stress may affect hepatocellular functions also by lowering the hepatocellular hydration state.

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.

Cell Volume Regulatory Responses of Isolated Perfused Rat Liver. The Effect of Amino Acids

1990 ◽  
Vol 371 (1) ◽  
pp. 493-502 ◽  
Author(s):  
Matthias WETTSTEIN ◽  
Stephan VOM DAHL ◽  
Florian LANG ◽  
Wolfgang GEROK ◽  
Dieter HÄUSSINGER
Keyword(s):  
Amino Acids ◽  
Cell Volume ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver

scholarly journals The effects of amino acids on albumin synthesis by the isolated perfused rat liver

1972 ◽  
Vol 129 (4) ◽  
pp. 805-809 ◽  
Author(s):  
L. Kelman ◽  
S. J. Saunders ◽  
S. Wicht ◽  
L. Frith ◽  
A. Corrigall ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Liver ◽  
Normal Values ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Albumin Synthesis ◽  
Isoleucine Leucine ◽  
Blood Concentrations ◽  
Normal Peripheral Blood

Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, α-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.

Bile Acid Metabolism in Mammals. V. Studies on the Sex Difference in the Response of the Isolated Perfused Rat Liver to Chenodeoxycholic Acid

1973 ◽  
Vol 51 (6) ◽  
pp. 418-423 ◽  
Author(s):  
I. M. Yousef ◽  
R. Magnusson ◽  
V. M. Price ◽  
M. M. Fisher
Keyword(s):  
Bile Acid ◽  
Sex Difference ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Bile Acid Metabolism ◽  
Isolated Perfused Rat Liver ◽  
Base Line ◽  
Female Rat ◽  
Perfused Rat Liver ◽  
Perfusion Medium

The hepatic metabolism of chenodeoxycholic acid (CDCA) was studied using the isolated perfused rat liver technique. In 12 perfusions, six male and six female, 30 μmol of CDCA were added to the perfusion medium, and in 12 other perfusions, also six of each sex, 1 μmol of CDCA was added to the perfusion medium. The CDCA was added after 2 h of base-line perfusion and the bile acids of liver, plasma, and bile were analyzed by combined thin-layer and gas chromatography. In the 2 h of perfusion prior to the addition of exogenous CDCA there were sex differences in the kinetics of bile acid secretion in the bile and in the bile acid composition of that bile. Following the addition of CDCA to the perfusion medium the female liver was found to take up more CDCA from the perfusion medium, to store more CDCA, and to convert less CDCA to β-muricholic acid. It was documented that the toxicity of CDCA for the isolated perfused liver of the female rat is not due to α- or β-muricholic acid, the end products of CDCA metabolism in the rat. The relatively greater capacity of the male liver to convert potentially toxic CDCA to nontoxic β-muricholic acid may explain, at least in part, the observed sex difference in CDCA hepatotoxicity.

scholarly journals Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin

1976 ◽  
Vol 160 (1) ◽  
pp. 85-95 ◽  
Author(s):  
J LaBadie ◽  
W A Dunn ◽  
N N Aronson
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Free Amino ◽  
Isolated Perfused Rat Liver ◽  
Methyl Groups ◽  
Second Derivative ◽  
Perfused Rat Liver ◽  
Lysine Residues ◽  
Derivatives Of ◽  
Hepatic Synthesis

The biosynthesis of carnitine in the rat was studied by following the metabolism of two radioactive derivatives of asialo-fetuin. The first contained 14C-labelled methyl groups covalently bound to the 6-N-amino fraction of its lysine residues as 6-N-monomethyl- and dimethyl-lysine. By treating this protein with iodomethane, a second derivative was produced in which the radioactivity was preferentially incorporated as 6-N-[Me-14C]-trimethyl-lysine. These desialylated glycoproteins, like other asialo-proteins, were immediately cleared from the blood by rat liver. Within hepatocyte lysosomes, the 14C-labelled proteins were rapidly hydrolysed, producing free amino acids containing the various 6-N-[Me-14C]methylated lysine residues. The radioactive amino acids crossed the lysosomal membrane and were further metabolized in the cytosol. Carnitine was the major radioactive metabolite detected in extracts of the rat carcass and liver after intravenous injection of 6-N-[Me-14C]trimethyl-lysine-labelled asialo-fetuin. Within 3h, at least 34.6% of the trimethyl-lysine in the administered protein was converted into carnitine. Similarly, an isolated perfused rat liver converted 30% of the added peptide-bound trimethyl-lysine into carnitine within 90 min. On the other hand, in numerous attempts we failed to detect radioactive carnitine in both rat liver and carcass between 20 min and 22 h after injection of 6-N-[Me-14C]-monomethyl- and -dimethyl-lysine-labelled asialo-fetuin. These data provide evidence for a pathway of carnitine biosynthesis that involves trimethyl-lysine as a peptide-bound precursor as proposed by R.A. Cox & C.L. Hoppel [(1973) Biochem. J. 136, 1083-1090] and V. Tanphaichitr & H.P. Broquist [(1973) J. Biol. Chem. 248, 2176-2181]. The findings also show that rat liver can synthesize carnitine without the aid of other tissues, but cannot convert free partially methylated lysines into trimethyl-lysine.

Cadmium transport in isolated perfused rat liver: zinc-cadmium competition

1979 ◽  
Vol 236 (3) ◽  
pp. C139-C143 ◽  
Author(s):  
B. S. Kingsley ◽  
J. M. Frazier
Keyword(s):  
Rat Liver ◽  
Biliary Excretion ◽  
Cadmium Uptake ◽  
Molar Ratio ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Transport Pathway ◽  
Cadmium Transport ◽  
Excess Zinc

The hypothesis that one component of cadmium uptake by rat hepatocytes involves a mediated transport pathway normally operative for zinc transport was tested in the isolated perfused rat liver preparation. Excess zinc in the perfusion medium suppressed cadmium uptake as indicated by the decrease in the normalized clearance (initial clearance divided by liver weight) from 0.340 +/- 0.019 (ml/min)/g in the presence of normal zinc concentrations (Zn:Cd molar ratio, 1.6) to 0.138 +/- 0.017 (ml/min)/g (Zn:Cd molar ratio, 13.0). In excess-zinc control experiments (no cadmium present) little zinc is accumulated by the liver, apparently due to competition between intrahepatic and extracellular binding. Exposure to cadmium increases both zinc secretion into the perfusion medium and biliary excretion of zinc. The effect at the sinusoidal membrane is probably a result of both the blockage of zinc resorption during cadmium uptake and the displacement of intrahepatic zinc. The effect on biliary excretion of zinc is due solely to displacement of intrahepatic zinc. These results are consistent with the proposed hypothesis for cadmium transport.

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