The Effect of Changes in Lactate Uptake on the Intracellular pH of the Perfused Rat Liver

1971 ◽  
Vol 41 (2) ◽  
pp. 159-170 ◽  
Author(s):  
R. D. Cohen ◽  
R. A. Iles ◽  
D. Barnett ◽  
M. E. O. Howell ◽  
J. Strunin
Keyword(s):  
Intracellular Ph ◽  
Rat Liver ◽  
Liver Cell ◽  
Direct Relationship ◽  
Control Mechanism ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Lactate Uptake ◽  
Simultaneous Change

1. Mean intracellular pH (pHi) and lactate have been measured simultaneously in the isolated perfused rat liver on two successive occasions separated by an interval of 20 min. In some experiments extra lactate was added to the perfusion medium immediately after the first measurement of pHi. 2. There was a direct relationship between the change in pHi over this interval and the simultaneous change of lactate uptake. 3. This finding is consistent with the hypothesis that lactate enters the liver cell at least partly in the ionized form and that its metabolism is accompanied by the effective production of hydroxyl ions. 4. These observations are discussed in terms of a possible control mechanism for lactate uptake by the liver.

The Effect of Simulated Metabolic Acidosis on Intracellular pH and Lactate Metabolism in the Isolated Perfused Rat Liver

1973 ◽  
Vol 45 (4) ◽  
pp. 543-549 ◽  
Author(s):  
M. H. Lloyd ◽  
R. A. Iles ◽  
B. R. Simpson ◽  
J. M. Strunin ◽  
J. M. Layton ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Rat Liver ◽  
Extracellular Ph ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Lactate Metabolism ◽  
Lactate Output ◽  
Lactate Uptake ◽  
The Relationship

1. The relationship between extracellular pH (pHe), intracellular pH (pHi) and lactate uptake was studied in the isolated perfused rat liver during simulated metabolic acidosis. 2. pHi fell to a considerably less extent than pHe when the latter was decreased from pH 7·4 to 6·7. 3. The liver took up lactate when pHi was greater than 7·0; at lower values of pHi lactate output occurred. 4. The relevance of these observations to the control of hepatic pHi and lactate metabolism is discussed.

Effect of Varying Pco2 on Intracellular pH and Lactate Consumption in the Isolated Perfused Rat Liver

1978 ◽  
Vol 55 (2) ◽  
pp. 175-181 ◽  
Author(s):  
P. G. Baron ◽  
R. A. Iles ◽  
R. D. Cohen
Keyword(s):  
Intracellular Ph ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Lactate Metabolism ◽  
Isolated Rat Liver ◽  
Buffering Effect ◽  
Lactate Uptake ◽  
Lactate Consumption ◽  
Isolated Rat

1. The effects of varying Pco2 on lactate uptake and intracellular pH (pHl) were studied in the isolated rat liver perfused with differing concentrations of lactate. 2. In general, pHl and lactate uptake are inversely related to Pco2, and pHl and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation. 3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues. 4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure.

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.

The Relation between Intracellular pH and Lactate Metabolism in the Isolated Perfused Rat Liver in Simulated Metabolic Acidosis

1973 ◽  
Vol 44 (6) ◽  
pp. 27P-27P ◽  
Author(s):  
M. H. Lloyd ◽  
R. A. Iles ◽  
B. R. Simpson ◽  
J. M. Strunin ◽  
R. D. Cohen
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Lactate Metabolism

scholarly journals NH4+ metabolism and the intracellular pH in isolated perfused rat liver

1993 ◽  
Vol 293 (3) ◽  
pp. 667-673 ◽  
Author(s):  
J Zange ◽  
J Gronczewski ◽  
A W H Jans
Keyword(s):  
Intracellular Ph ◽  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Isolated Perfused Rat Liver ◽  
Small Range ◽  
Perfused Rat Liver ◽  
Atp Content ◽  
Intracellular Acidification ◽  
Subsequent Conversion ◽  
Intracellular Alkalinization

The effects of NH4+ on the intracellular pH (pHi) and on the ATP content in isolated perfused rat liver were studied by 31P n.m.r. spectroscopy. In the initial phase of perfusion an average pHi of 7.29 +/- 0.04 was estimated. The presence of low (0.5 mmol/l) and high (10 mmol/l) doses of NH4Cl induced significant intracellular acidification by -0.06 +/- 0.03 and -0.11 +/- 0.03 pH unit respectively. This effect was in contrast with the transient intracellular alkalinization observed in preliminary studies on isolated hepatocytes, which was caused by a passive entry of NH3 by non-ionic diffusion and subsequent conversion into NH4+. During application of 0.5 mmol/l NH4Cl the liver released 0.54 +/- 0.06 mumol of urea/min per g into the perfusate. When the intracellular availability of HCO3- was decreased by acetazolamide (0.5 mmol/l) or by removal of HCO3- from the perfusion medium, the decrease in pHi by NH4Cl application was significantly lower than under control conditions. Furthermore, synthesis of urea was significantly inhibited by the decrease in intracellular HCO3-. Under these conditions, 10 mmol/l NH4Cl caused the transient alkalinization that was expected because of the passive uptake of uncharged NH3. Therefore, it is concluded that the intracellular acidification induced by NH4Cl is caused by the continuous utilization of intracellular HCO3- via the synthesis of urea. This metabolic effect on pHi dominates the effects of passive NH3 entry. The rate of urea formation depends on continuous efflux of H+, which is strictly limiting the degree of intracellular acidification within a small range. If the extrusion of H+ by the Na+/H+ exchanger was inhibited by amiloride (0.5 mmol/l) during the NH4Cl application, the decrease in pHi was amplified and the formation of urea was significantly inhibited. The application of NH4Cl at 0.5 or 10 mmol/l decreased the ATP content by 11% or 22% respectively.

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.

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.

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.

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