scholarly journals Hormonal and ionic control of the glycogenolytic cascade in rat liver

1977 ◽  
Vol 162 (1) ◽  
pp. 135-142 ◽  
Author(s):  
G van de Werve ◽  
L Hue ◽  
H G Hers
Keyword(s):  
Rat Liver ◽  
Incubation Medium ◽  
Liver Extract ◽  
Isolated Hepatocytes ◽  
Phosphorylase Kinase ◽  
High Concentration ◽  
Unanesthetized Animals ◽  
Histone Kinase ◽  
Dose Dependent

1. A parallel dose-dependent activation of histone kinase, phosphorylase kinase and phosphorylase was observed in isolated hepatocytes incubated in the presence of glucagon; the effect of suboptimal concentrations of glucagon was antagonized by insulin. 2. An activation of phosphorylase which was not accompanied by a stable change in the activity of phosphorylase kinase was observed in hepatocytes incubated with phenylephrine, isoproterenol or vasopressin as well as on decapitation of unanesthetized animals. A dissociation of the two enzymic activities was also observed in hepatocytes incubated in the presence of a high concentration of glucose, in which phosphorylase was strongly inactivated with no change in the activity of phosphorylase kinase. 3. The activation of phosphorylase by phenylephrine in isolated hepatocytes was counteracted by insulin, greatly decreased by the absence of Ca2+ from the incubation medium, and completely suppressed by the replacement of Na+ by K+. 4. In a liver extract, phosphorylase kinase could also be activated by trypsin. Control, glucagon-activated or trypsin-activated phosphorylase kinase was inhibited by about 70% by EGTA and the activity was restored by the addition of Ca2+. 5. The mechanisms that control the activity of phosphorylase kinase and of phosphorylase are discussed.

scholarly journals Mechanism of activation of glycogen phosphorylase by fructose in the liver. Stimulation of phosphorylase kinase related to the consumption of adenosine triphosphate

1979 ◽  
Vol 178 (1) ◽  
pp. 119-126 ◽  
Author(s):  
G Van de Werve ◽  
H G Hers
Keyword(s):  
High Speed ◽  
Glycogen Phosphorylase ◽  
Isolated Hepatocytes ◽  
Phosphorylase Kinase ◽  
Free Medium ◽  
Histone Kinase ◽  
Dose Dependent ◽  
High Speed Supernatant ◽  
Stimulation Of

1. A dose-dependent activation of phosphorylase and consumption of ATP was observed in isolated hepatocytes incubated in the presence of fructose; histone kinase and phosphorylase kinase activities were unchanged at doses of this sugar that were fully effective on phosphorylase. The activation of phosphorylase by fructose was also observed in cells incubated in a Ca2+-free medium as well as in the livers of rats in vivo. 2. In a liver high-speed supernatant, fructose, tagatose and sorbose stimulated the activity of phosphorylase kinase; this effect was dependent on the presence of K+ ions, which are required for the activity of fructokinase; it was accompanied by the transformation of ATP into ADP. In the presence of hexokinase, glucose also stimulated phosphorylase kinase, both in an Na+ or a K+ medium. 3. The activities of partially purified muscle or liver phosphorylase kinase were unchanged in the presence of fructose. 4. Some properties of liver phosphorylase kinase are described, including a high molecular weight and an inhibition at ATP/Mg ratios above 0.5, as well as an effect of ATP concentration on the hysteretic behaviour of this enzyme. 5. The effect of fructose on the activation of phosphorylase is discussed in relation to the comsumption of ATP.

scholarly journals Effect of micromolar concentrations of manganese ions on calcium-ion cycling in rat liver mitochondria

1983 ◽  
Vol 212 (3) ◽  
pp. 773-782 ◽  
Author(s):  
B P Hughes ◽  
J H Exton
Keyword(s):  
Rat Liver ◽  
Calcium Ion ◽  
Incubation Medium ◽  
Liver Mitochondria ◽  
Ruthenium Red ◽  
Rat Liver Mitochondria ◽  
Manganese Ions ◽  
Dose Dependent Decrease ◽  
Incubation Temperatures ◽  
Dose Dependent

The effects of micromolar concentrations of Mn2+ on the rat liver mitochondrial Ca2+ cycle were investigated. It was found that the addition of Mn2+ to mitochondria which were cycling 45Ca2+ led to a rapid dose dependent decrease in the concentration of extramitochondrial 45Ca2+ of about 1 nmol/mg of protein. The effect was complete within 30 s, was half maximal with 10 microM Mn2+ and was observed in the presence of 3 mM Mg2+ and 1 mM ATP. It occurred over a broad range of incubation temperatures, pH and mitochondrial Ca2+ loads. It was not observed when either Mg2+ or phosphate was absent from the incubation medium, or in the presence of Ruthenium Red. These findings indicate that micromolar concentrations of Mn2+ stimulate the uptake of Ca2+ by rat liver mitochondria, and provide evidence for an interaction between Mg2+ and Mn2+ in the control of mitochondrial Ca2+ cycling.

scholarly journals Control of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle in isolated hepatocytes by glucose and glucagon. Role of a low-molecular-weight stimulator of phosphofructokinase

1980 ◽  
Vol 192 (3) ◽  
pp. 887-895 ◽  
Author(s):  
Emile Van Schaftingen ◽  
Louis Hue ◽  
Henri-Géry Hers
Keyword(s):  
Molecular Weight ◽  
Incubation Medium ◽  
Liver Extract ◽  
Gel Filtration ◽  
Isolated Hepatocytes ◽  
Low Molecular Weight ◽  
Experimental Conditions ◽  
Fructose 1,6 Bisphosphate ◽  
Acid Labile

1. Recycling of metabolites between fructose 6-phosphate and triose phosphates has been investigated in isolated hepatocytes by the randomization of carbon between C(1) and C(6) of glucose formed from [1-14C]galactose. 2. Randomization of carbon atoms was regularly observed with hepatocytes isolated from fed rats and was then little influenced by the concentration of glucose in the incubation medium. It was decreased by about 50% in the presence of glucagon. 3. Randomization of carbon atoms by hepatocytes isolated from starved rats was barely detectable at physiological concentrations of glucose in the incubation medium, but was greatly increased with increasing glucose concentrations. It was nearly completely suppressed by glucagon. These large changes can be attributed to parallel variations in the activity of phosphofructokinase. 4. The main factors that appear to control the activity of phosphofructokinase under these experimental conditions are the concentration of fructose 6-phosphate, the concentration of fructose 1,6-bisphosphate and also the affinity of the enzyme for fructose 6-phosphate. 5. The affinity of phosphofructokinase for fructose 6-phosphate was diminished by incubation of the cells in the presence of glucagon and also by filtration of an extract of hepatocytes through Sephadex G-25 and by purification of the enzyme. When assayed at 0.25 or 0.5mm-fructose 6-phosphate, the activity of phosphofructokinase present in a liver Sephadex filtrate was increased by a low-molecular-weight effector, which could be isolated from a liver extract by ultrafiltration, gel filtration or heat treatment, but was rapidly destroyed in trichloroacetic acid, even in the cold. This effector appears to be a highly acid-labile phosphoric ester. Its concentration was greatly increased in hepatocytes incubated in the presence of glucose and was decreased in the presence of glucagon.

scholarly journals Characteristics of the desensitization and resensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells

1982 ◽  
Vol 208 (2) ◽  
pp. 317-322 ◽  
Author(s):  
S Keppens ◽  
H De Wulf
Keyword(s):  
Cyclic Amp ◽  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Liver Cells ◽  
Adrenergic Agonists ◽  
Tentative Model ◽  
Rat Liver Cells ◽  
Specific Antagonist ◽  
Dose Dependent

Vasopressin and alpha-adrenergic agonists were shown previously [Bréant, Keppens & De Wulf (1981) Biochem. J. 200, 509-514] to induce a heterologous, dose-dependent and receptor-mediated desensitization of the cyclic AMP-independent glycogenolytic response in isolated hepatocytes. The desensitized state of the hepatocytes can be preserved as long as the agonist is bound to its receptor. Conversely, washing the cells with a hormone-free buffer or displacement of the agonist from its receptor by a specific antagonist restores the responsiveness. The desensitization and its reversibility (i.e. resensitization) are obtained within minutes. The desensitization can be clearly elicited at temperatures as low as 5 degrees C, whereas the glycogenolytic response and the enhancement of the 45Ca flux are only obtained above 15 degrees C; the resensitization requires even higher temperatures. A tentative model is proposed to account for the observed effects.

Hepatic uptake of intact glutathione S-conjugate, inhibition by organic anions, and sinusoidal catabolism

1993 ◽  
Vol 265 (3) ◽  
pp. G547-G554
Author(s):  
C. A. Hinchman ◽  
A. T. Truong ◽  
N. Ballatori
Keyword(s):  
Guinea Pig ◽  
Rat Liver ◽  
Marked Decrease ◽  
Hepatic Uptake ◽  
Half Time ◽  
High Concentrations ◽  
Rat Livers ◽  
Dose Dependent ◽  
Uptake And Metabolism ◽  
Guinea Pig Liver

To identify potential mechanisms for hepatic removal of circulating glutathione (GSH) conjugates, uptake and metabolism of S-2,4-dinitrophenylglutathione (DNP-SG) were examined in isolated perfused livers from rat and guinea pig. Guinea pig livers perfused with 5 mumol of DNP-SG in a recirculating system (50 microM initial concn) rapidly cleared the conjugate from the perfusate (half time 3.7 min), whereas clearance was considerably slower in rat liver (half time 35 min). Disappearance of DNP-SG from the perfusate was accompanied by a simultaneous appearance of DNP-SG and its metabolites in bile. Addition of acivicin, an inhibitor of gamma-glutamyltransferase (gamma-GT), to the perfusate resulted in a marked decrease in DNP-SG clearance by guinea pig liver but had no effect in rat liver, suggesting that in the guinea pig this process is largely dependent on sinusoidal gamma-GT activity. However, even in the presence of acivicin, rat and guinea pig livers removed nearly one-half of the administered DNP-SG from the recirculating perfusate over 30 min. High concentrations of DNP-SG were found in bile (up to 3.7 mM), indicating that the liver is capable of transporting the intact conjugate from the circulation. When rat livers were perfused with higher concentrations of DNP-SG (100 and 250 microM), biliary excretion of DNP-SG increased dose dependently, with concentrations in bile reaching 10 mM at the higher dose. This was accompanied by a dose-dependent choleresis.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Regulation of rat liver glycogen synthase. Roles of Ca2+, phosphorylase kinase, and phosphorylase a.

1983 ◽  
Vol 258 (9) ◽  
pp. 5490-5497
Author(s):  
W G Strickland ◽  
M Imazu ◽  
T D Chrisman ◽  
J H Exton
Keyword(s):  
Rat Liver ◽  
Glycogen Synthase ◽  
Liver Glycogen ◽  
Phosphorylase Kinase

scholarly journals Purification of rat liver phosphorylase kinase.

1982 ◽  
Vol 257 (18) ◽  
pp. 10798-10804 ◽  
Author(s):  
T D Chrisman ◽  
J E Jordan ◽  
J H Exton
Keyword(s):  
Rat Liver ◽  
Phosphorylase Kinase

Autoregulation of 3, 3′,5′-triiodothyronine production by rat liver microsomes

1981 ◽  
Vol 98 (2) ◽  
pp. 240-245 ◽  
Author(s):  
T. Kaminski ◽  
J. Köhrle ◽  
R. Ködding ◽  
R.-D. Hesch
Keyword(s):  
Rat Liver ◽  
Incubation Medium ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Incubation Mixture ◽  
Rat Liver Microsomes ◽  
Experimental Conditions ◽  
Physiological Concentration ◽  
Enzyme Binding ◽  
Ph Dependent

Abstract. Conversion of thyroxine (T4) to 3,3′,5′-triiodothyronine (rT3) was studied in rat liver microsomes. Addition of rT3 at a physiological concentration to the incubation medium inhibited the deiodination of thyroxine to rT3. With a concentration of rT3 greater than 37.6 nM no net rT3 production at pH 8.0 was observed. Further increases in rT3 concentration resulted only in degradation of added rT3 and no net synthesis of rT3 from T4 could be detected. The inhibitory effect of rT3 upon its own production from T4 was pH dependent, 5 fold lower amounts of hormone being required to inhibit completely rT3 production at pH 7.4 than at pH 8.0. With the same experimental conditions no significant effect of rT3 on the conversion of T4 to 3,5,3′-triiodothyronine (T3) could be observed at pH 8.0 with all concentrations of added iodothyronine. A linear production of 3,3′-T2 from added rT3 was determined over the whole range of rT3 concentration, suggesting a lack of saturation of deiodinating enzyme. Binding of rT3 by anti-rT3 antibody added to the incubation mixture enhanced rT3 production from T4 by protecting rT3 from being degraded and/or diminishing the inhibitory effect of this iodothyronine on its own production. It was concluded that rT3 influenced its own production and that this effect may represent an important autoregulatory process in the iodothyronine metabolism.

ANALYSIS OF MT2A AND MT3 GENE EXPRESSION IN RAT'S LIVER AND KIDNEY IN RESPONSE TO CADMIUM CHLORIDE POISONING

2021 ◽  
pp. 38-42
Author(s):  
M. M. Ziatdinova ◽  
T. G. Yakupova ◽  
Ya. V. Valova ◽  
G. F. Mukhammadieva ◽  
D. O. Karimov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
Cadmium Chloride ◽  
Transcriptional Activity ◽  
Female Rats ◽  
Expression Level ◽  
Cadmium Poisoning ◽  
Liver And Kidney ◽  
Dose Dependent ◽  
Higher Doses

The aim of this study was to investigate the expression of metallothionein genes in the liver and kidneys of rats with acute cadmium poisoning.Simulation of poisoning with cadmium chloride was carried out on white outbred female rats, divided into 4 groups depending on the dose of the injected toxicant. RNA samples isolated from rat liver and kidneys were used as research materials.The multiplicity of expression of the MT3 gene in the kidneys increased at the lowest dose of CdCl2 , which was used in this experiment (0.029 mg / kg); with increasing dosage, the expression level decreased, but not lower than the control values. Analysis of the expression of the same gene in the liver showed a tendency towards a decrease in the content of transcripts with increasing dose. The frequency of expression of the MT2A gene at higher doses of CdCl2 increased both in the liver and in the kidneys.In the present work, statistically significant dose-dependent changes in the expression multiplicity of metallothionein genes were detected 24 hours after CdCl2 administration. The revealed differences in the level of transcriptional activity of metallothionein genes require further investigation, since there are probably differences in the level of gene expression at earlier and later periods of toxicant action.

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