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.

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.

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

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.

Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver

Hepatology ◽  
1992 ◽  
Vol 15 (1) ◽  
pp. 107-116 ◽  
Author(s):  
Michael H. Nathanson ◽  
Anil Gautam ◽  
Rafael Bruck ◽  
Carlos M. Isales ◽  
James L. Boyer
Keyword(s):  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Bile Secretion ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver

Oxygen consumption by rat liver: effects of taurocholate and sulfobromophthalein transport, glucagon, and cation substitution

1983 ◽  
Vol 244 (5) ◽  
pp. G523-G531
Author(s):  
R. W. van Dyke ◽  
J. L. Gollan ◽  
B. F. Scharschmidt
Keyword(s):  
Oxygen Consumption ◽  
Rat Liver ◽  
Large Fraction ◽  
Isolated Hepatocytes ◽  
Rectal Gland ◽  
Isolated Perfused Rat Liver ◽  
Cation Substitution ◽  
Perfused Rat Liver ◽  
Oxygen Utilization ◽  
Bile Formation

The proportion of total hepatic energy utilized for bile formation and transport of taurocholate (TC) and conjugated sulfobromophthalein (cBSP) has not been defined previously. To study this question we have measured changes in oxygen consumption by the isolated perfused rat liver and freshly isolated hepatocytes occurring in response to TC and cBSP administration, cation substitution, and glucagon infusion. The basal rates of bile formation and oxygen consumption varied considerably among different livers, and there was little or no relationship between these two variables. Administration of either TC or cBSP to the perfused liver elicited a marked choleresis but failed to alter steady-state oxygen consumption even at maximal rates of TC or cBSP transport. Similarly, incubation of hepatocytes with TC or cBSP did not alter oxygen consumption. In contrast, inhibition of Na-K-ATPase by removal of sodium and/or potassium from the medium reduced oxygen consumption by perfused rat liver and isolated hepatocytes by 27-37%, and glucagon administration increased oxygen consumption in both systems by 31-40%. These findings indicate that the oxygen requirement for bile formation and even maximal rates of TC and cBSP transport is small compared with that for the metabolic changes induced by glucagon or for hepatic Na-K-ATPase activity. This is in contrast to other epithelial tissues, such as kidney and rectal gland, in which oxygen utilization for transepithelial solute and water transport constitutes a large fraction of both total and Na-K-ATPase-dependent oxygen consumption.

A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver

1982 ◽  
Vol 47 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Yoav Sharoni ◽  
Maria C Topal ◽  
Patricia R Tuttle ◽  
Henry Berger
Keyword(s):  
Rat Liver ◽  
Isoelectric Point ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Plasminogen Activators ◽  
Rat Plasma ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Molecular Weights ◽  
Physiological Relevance

SummaryOf the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.

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