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 ◽  
...  

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.

1978 ◽  
Vol 55 (2) ◽  
pp. 175-181 ◽  
Author(s):  
P. G. Baron ◽  
R. A. Iles ◽  
R. D. Cohen

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.


1973 ◽  
Vol 44 (6) ◽  
pp. 27P-27P ◽  
Author(s):  
M. H. Lloyd ◽  
R. A. Iles ◽  
B. R. Simpson ◽  
J. M. Strunin ◽  
R. D. Cohen

1971 ◽  
Vol 41 (2) ◽  
pp. 159-170 ◽  
Author(s):  
R. D. Cohen ◽  
R. A. Iles ◽  
D. Barnett ◽  
M. E. O. Howell ◽  
J. Strunin

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.


1993 ◽  
Vol 293 (3) ◽  
pp. 667-673 ◽  
Author(s):  
J Zange ◽  
J Gronczewski ◽  
A W H Jans

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.


1982 ◽  
Vol 47 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Yoav Sharoni ◽  
Maria C Topal ◽  
Patricia R Tuttle ◽  
Henry Berger

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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