scholarly journals The mechanism by which adenosine decreases gluconeogenesis from lactate in isolated rat hepatocytes

1987 ◽  
Vol 246 (2) ◽  
pp. 449-454 ◽  
Author(s):  
A Lavoinne ◽  
H A Buc ◽  
S Claeyssens ◽  
M Pinosa ◽  
F Matray
Keyword(s):  
Ketone Body ◽  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
Adenosine Kinase ◽  
Isolated Rat Hepatocytes ◽  
Adenosine Deaminase 2 ◽  
Body Production ◽  
Gluconeogenic Substrates ◽  
Isolated Rat ◽  
Stimulation Of

Incubation of hepatocytes from 24 h-starved rats in the presence of 0.5 mM-adenosine decreased gluconeogenesis from lactate, but not from alanine. The inhibition of gluconeogenesis was associated with a stimulation of ketone-body production and an inhibition of pyruvate oxidation. These metabolic changes were suppressed in the presence of iodotubercidin (an inhibitor of adenosine kinase), but were reinforced in the presence of deoxycoformycin (an inhibitor of adenosine deaminase); 2-chloroadenosine induced no change in gluconeogenesis from lactate. These data indicate that the inhibition of gluconeogenesis by adenosine probably results from its conversion into adenine nucleotides. In the presence of lactate or pyruvate, but not with alanine or asparagine, this conversion resulted in a decrease in the [ATP]/[ADP] ratio in both mitochondrial and cytosolic compartments. Adenosine decreased the Pi concentration with all gluconeogenic substrates.

scholarly journals Homocysteine enhances the inhibitory effect of extracellular adenosine on the synthesis of proteins in isolated rat hepatocytes

1995 ◽  
Vol 310 (3) ◽  
pp. 893-896 ◽  
Author(s):  
S Tinton ◽  
P Buc-Calderon
Keyword(s):  
Protein Synthesis ◽  
Kinase Inhibitor ◽  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Adenosine Kinase ◽  
Isolated Rat Hepatocytes ◽  
Extracellular Adenosine ◽  
Inhibition Of Protein Synthesis ◽  
Isolated Rat

Previous work has shown that extracellular adenosine inhibits the incorporation of radiolabelled leucine into proteins in isolated rat hepatocytes [Tinton, Lefebvre, Cousin and Buc Calderon (1993) Biochim. Biophys. Acta 1176, 1-6]. In this study, we investigated whether its metabolism into adenine nucleotides, inosine or S-adenosylhomocysteine (AdoHcy) is required to induce such an impairment. Incubation of isolated hepatocytes in the presence of adenosine at 0.5 or 1 mM reduces the synthesis of proteins by about 45% after 120 min of incubation. Such an inhibition occurred without cell lysis and was not modified by adding the adenosine kinase inhibitor 5-iodotubercidin (15 microM) or the adenosine deaminase inhibitor coformycin (0.1 microM). It is therefore unlikely that the anabolic and catabolic pathways of adenosine are involved in the inhibition of protein synthesis. Adenosine (1 mM) increased the level of AdoHcy and S-adenosylmethionine by 20- and 5-fold respectively after 60 min of incubation and reduced the methylation index. These events as well as the inhibition of protein synthesis were strongly enhanced in the presence of L-homocysteine (2 mM). It is therefore concluded that the metabolism of adenosine into AdoHcy, which is known to be a potent inhibitor of cellular methylation reactions, may play an important role in the control of translation.

scholarly journals Mechanisms of elevation of adenosine levels in anoxic hepatocytes

1993 ◽  
Vol 290 (3) ◽  
pp. 671-677 ◽  
Author(s):  
F Bontemps ◽  
M F Vincent ◽  
G Van den Berghe
Keyword(s):  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
Adenosine Kinase ◽  
Slight Effect ◽  
Isolated Rat Hepatocytes ◽  
Adenosylhomocysteine Hydrolase ◽  
Adenosine Concentration ◽  
Isolated Rat ◽  
Rate Of Accumulation ◽  
In Cells

Previous work has shown that normoxic isolated rat hepatocytes continuously produce adenosine from AMP and that the nucleoside is not catabolized further but immediately rephosphorylated by adenosine kinase [Bontemps, Van den Berghe and Hers (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2829-2833]. We now report the effect of anoxia on adenosine production and on the AMP/adenosine substrate cycle. In cell suspensions incubated in O2/CO2, the adenosine concentration was about 0.4 microM. It increased 30-fold in cells incubated in N2/CO2 or with 5 mM KCN, and 20-fold in cells incubated with 2 mM amytal. Adenosine production, measured in hepatocytes in which adenosine kinase and adenosine deaminase were inhibited by 5-iodotubercidin and deoxycoformycin respectively, was about 18 nmol/min per g of cells in normoxia; it increased about 2-fold in anoxia, although AMP increased 8-16-fold in this condition. From studies with inhibitors of membrane 5′-nucleotidase and of S-adenosylhomocysteine hydrolase, it was deduced that adenosine is produced by the latter enzyme and by cytosolic 5′-nucleotidase in normoxia, and by cytosolic and membrane 5′-nucleotidases in anoxia. Unlike in normoxic hepatocytes, inhibition of adenosine kinase by 5-iodotubercidin neither elevated the adenosine concentration nor enhanced total purine release from adenine nucleotides in cells treated with N2/CO2 or KCN; it had only a slight effect in cells treated with amytal. This indicates that recycling of adenosine is suppressed or profoundly inhibited in anoxia. The rate of accumulation of adenosine in anoxia was several-fold lower than the rate of its rephosphorylation upon reoxygenation. It is concluded that the elevation of adenosine in anoxic hepatocytes is much more dependent on decreased recycling of adenosine by adenosine kinase than on increased production by dephosphorylation of AMP.

scholarly journals Effect of adenosine and inosine on ureagenesis in hepatocytes

1987 ◽  
Vol 245 (2) ◽  
pp. 371-374 ◽  
Author(s):  
R Guinzberg P ◽  
I Laguna ◽  
A Zentella ◽  
R Guzman ◽  
E Piña
Keyword(s):  
Uric Acid ◽  
Rat Hepatocytes ◽  
Physiological Significance ◽  
Isolated Rat Hepatocytes ◽  
Dose Dependent ◽  
Isolated Rat ◽  
Stimulation Of

Adenosine and inosine produced a dose-dependent stimulation of ureagenesis in isolated rat hepatocytes. Hypoxanthine, xanthine and uric acid were without effect. Half-maximally effective concentrations were 0.08 microM for adenosine and 5 microM for inosine. Activation of ureagenesis by both nucleosides had the following characteristics: (a) it was observed with either glutamine or (NH4)2CO3, provided that glucose was present; (b) it was not detected when glucose was replaced by lactate plus oleate; (c) it was mutually antagonized by glucagon, but not by adrenaline; and (d) it was dependent on Ca2+. We suggest that the action of adenosine and inosine on ureagenesis might be of physiological significance.

α1B-Adrenoceptor-mediated stimulation of Ca2+ mobilization and cAMP accumulation in isolated rat hepatocytes

1993 ◽  
Vol 246 (2) ◽  
pp. 113-120 ◽  
Author(s):  
Takahide Nomura ◽  
Haruhito Kondo ◽  
Seiko Hasegawa ◽  
Toshiko Watanabe ◽  
Rie Yokoyama ◽  
...  
Keyword(s):  
Rat Hepatocytes ◽  
Camp Accumulation ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat ◽  
Stimulation Of

Nuclear Accumulation of G-Actin in Isolated Rat Hepatocytes by Adenine Nucleotides

1997 ◽  
Vol 240 (3) ◽  
pp. 697-700 ◽  
Author(s):  
Irma Meijerman ◽  
W.Marty Blom ◽  
Hans J.G.M. de Bont ◽  
Gerard J. Mulder ◽  
J.Fred Nagelkerke
Keyword(s):  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
Nuclear Accumulation ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat
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