scholarly journals Rapid Ca2+ influx induced by the action of dibutylhydroquinone and glucagon in the perfused rat liver

1997 ◽  
Vol 323 (2) ◽  
pp. 463-467 ◽  
Author(s):  
Tanya L. APPLEGATE ◽  
Ari KARJALAINEN ◽  
Fyfe L. BYGRAVE
Keyword(s):  
Endoplasmic Reticulum ◽  
Electron Transport ◽  
Rat Liver ◽  
Sodium Azide ◽  
Isolated Hepatocytes ◽  
Atp Depletion ◽  
Perfused Rat Liver ◽  
Total Calcium ◽  
Combined Administration ◽  
Prior Administration

Glucagon induces a slight Ca2+ efflux when administered to the perfused rat liver. However, the hormone promotes rapid and significant Ca2+ influx after the prior administration of 2,5-di(t-butyl)-1,4-hydroquinone (BHQ), an agent that promotes Ca2+ release from the endoplasmic reticulum (ER). The concentrations of glucagon that promote Ca2+ influx are similar to those that promote glycogenolysis and gluconeogenesis in isolated hepatocytes. The permeable analogue of cAMP, but not that of cGMP, is able to duplicate the Ca2+-mobilizing effects of glucagon. The influx of Ca2+ into liver is blocked by Ni2+. Administration of sodium azide, an inhibitor of mitochondrial electron transport, also blocks the BHQ plus glucagon-induced Ca2+ influx and this is reversed when azide administration is terminated. The actions of azide are evident within 60 s after administration or withdrawal, and also occur when either oligomycin or fructose is co-administered; this provides evidence for an effect of azide independent of cellular ATP depletion. Measurement of total calcium in mitochondria that were isolated rapidly from perfused livers after the combined administration of glucagon and BHQ confirmed that large quantities of extracellular Ca2+ had entered these organelles. These experiments provide evidence that in the perfused rat liver the artificial emptying of the ER Ca2+ pool allows glucagon to promote rapid and sustained Ca2+ influx that seems to terminate in mitochondria.

Enhanced cytotoxicity of imidacloprid by biotransformation in isolated hepatocytes and perfused rat liver

2020 ◽  
Vol 164 ◽  
pp. 183-190
Author(s):  
Paulo F.V. Bizerra ◽  
Anilda R.J.S. Guimarães ◽  
Camila A. Miranda ◽  
Rodrigo P. Constantin ◽  
Karina S. Utsunomiya ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Perfused Rat Liver

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.

scholarly journals Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver

1992 ◽  
Vol 281 (2) ◽  
pp. 387-392 ◽  
Author(s):  
Y Hamada ◽  
A Karjalainen ◽  
B A Setchell ◽  
J E Millard ◽  
F L Bygrave
Keyword(s):  
Oxygen Uptake ◽  
Rat Liver ◽  
Bile Flow ◽  
Bile Secretion ◽  
Perfused Rat Liver ◽  
Diseased Liver ◽  
Glucose Output ◽  
Opposing Effects ◽  
Prior Administration ◽  
Slow Onset

Changes in perfusate Ca2+ (measured with a Ca(2+)-selective electrode) and changes in bile calcium (measured by atomic absorption spectroscopy) were continuously and simultaneously monitored after infusion of (a) vasopressin, (b) glucagon and (c) both vasopressin and glucagon together to the perfused rat liver. Also monitored were perfusate glucose and oxygen concentrations and bile flow. Vasopressin induces a sharp, transient, pulse of increased bile flow and increased bile calcium within 1 min of infusion, concomitant with rapid changes in perfusate Ca2+ fluxes, glucose output and oxygen uptake. This is immediately followed by a decrease in both bile flow and bile calcium for as long as the hormone is administered. Changes induced by glucagon are a relatively slow onset of perfusate Ca2+ efflux and oxygen uptake, but rapid glucose output, and a small but significant and transient decrease in bile flow and bile calcium which, despite the continued infusion of the hormone, spontaneously and rapidly returns to normality. However, the greatest responses are observed after co-administration of both hormones. Coincident with the augmented perfusate Ca2+ fluxes (influx) seen in earlier work, there occurs within 1 min of vasopressin infusion a sharp increase in bile secretion and bile calcium greater in magnitude than that produced by vasopressin alone. Immediately thereafter bile secretion and bile calcium decline below basal values and remain there for as long as the hormones are administered. Glucagon and vasopressin therefore each have opposing effects on bile flow and bile calcium. However, the action of vasopressin is enhanced by the prior administration of glucagon. The data thus reveal features about the actions of glucagon and Ca(2+)-mobilizing hormones on bile flow and bile calcium not previously recorded and provide a novel framework around which the whole issue of hepato-biliary Ca2+ homoeostasis can be assessed in normal and diseased liver.

Effect of indomethacin on the uptake, metabolism and excretion of 3-oxocholic acid: Studies in isolated hepatocytes and perfused rat liver

1991 ◽  
Vol 1084 (3) ◽  
pp. 247-250 ◽  
Author(s):  
H. Takikawa ◽  
J.C. Fernandez-Checa ◽  
J. Kuhlenkamp ◽  
A. Stolz ◽  
M. Ookhtens ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Perfused Rat Liver

Metabolism of maltose in perfused rat liver and in isolated hepatocytes

1976 ◽  
Vol 168 (3) ◽  
pp. 157-163 ◽  
Author(s):  
U. Sprandel ◽  
G. Wolfram ◽  
R. Scholz
Keyword(s):  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Perfused Rat Liver

Eicosanoids released following inhibition of the endoplasmic reticulum Ca2+ pump stimulate Ca2+ efflux in the perfused rat liver

1993 ◽  
Vol 45 (11) ◽  
pp. 2209-2214 ◽  
Author(s):  
Juan Llopis ◽  
Geoffrey C. Farrell ◽  
Steven K. Duddy ◽  
George E.N. Kass ◽  
Annie Gahm ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Rat Liver ◽  
Perfused Rat Liver

scholarly journals Inhibition of proteolysis by cell swelling in the liver requires intact microtubular structures

1995 ◽  
Vol 308 (2) ◽  
pp. 529-536 ◽  
Author(s):  
S vom Dahl ◽  
B Stoll ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Cell Volume ◽  
Rat Liver ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Cell Swelling ◽  
Perfused Rat Liver ◽  
Volume Changes ◽  
Isolated Rat Hepatocytes ◽  
Microtubule Inhibitors ◽  
Microtubular Structures

In the perfused rat liver, proteolysis is inhibited by cell swelling in response to hypo-osmotic media, glutamine and insulin. Colchicine, an inhibitor of microtubules, did not affect cell swelling in response to these agonists. However, the antiproteolytic action of these effectors was largely blunted in the presence of colchicine or the microtubule inhibitors colcemid and taxol. On the other hand, inhibition of proteolysis by phenylalanine, asparagine or NH4Cl, i.e. compounds which exert their antiproteolytic effects by mechanisms distinct from cell swelling, was not sensitive to colchicine. Swelling-induced inhibition of proteolysis was not affected by cytochalasin B. The anti-proteolytic effect of hypo-osmotic cell swelling and insulin was largely abolished in freshly isolated rat hepatocytes; however, it reappeared upon cultivation of the hepatocytes for 6-10 h. The restoration of the sensitivity of proteolysis to cell volume changes was accompanied by a progressive reorganization of microtubule structures, as shown by immunohistochemical staining for tubulin. It is concluded that intact microtubules are required for the control of proteolysis by cell volume, but not for the control of proteolysis by phenylalanine, asparagine or NH4Cl. These findings may explain why others [Meijer, Gustafson, Luiken, Blommaart, Caro, Van Woerkom, Spronk and Boon (1993) Eur. J. Biochem. 215, 449-454] failed to detect an antiproteolytic effect of hypo-osmotic exposure of freshly isolated hepatocytes. This effect, however, which is consistently found in the intact perfused rat liver, also reappeared in isolated hepatocytes when they were allowed to reorganize their microtubular structures in culture.

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