scholarly journals Phosphatidylinositol metabolism in rat hepatocytes stimulated by vasopressin

1981 ◽  
Vol 194 (1) ◽  
pp. 155-165 ◽  
Author(s):  
C J Kirk ◽  
R H Michell ◽  
D A Hems
Keyword(s):  
Glycogen Phosphorylase ◽  
Equilibrium Distribution ◽  
Rat Hepatocytes ◽  
Subcellular Fractionation ◽  
Isolated Rat Hepatocytes ◽  
Phosphatidylinositol Metabolism ◽  
Maximal Activation ◽  
Vasopressin Receptors ◽  
Stimulation Of

In isolated rat hepatocytes, vasopressin evoked a large increase in the incorporation of [32P]Pi into phosphatidylinositol, accompanied by smaller increases in the incorporation of [1-14C]oleate and [U-14C]glycerol. Incorporation of these precursors into the other major phospholipids was unchanged during vasopressin treatment. Vasopressin also promoted phosphatidylinositol breakdown in hepatocytes. Half-maximum effects on phosphatidylinositol breakdown and on phosphatidylinositol labelling occurred at about 5 nM-vasopressin, a concentration at which approximately half of the hepatic vasopressin receptors are occupied but which is much greater than is needed to produce half-maximal activation of glycogen phosphorylase. Insulin did not change the incorporation of [32P]Pi into the phospholipids of hepatocytes and it had no effect on the response to vasopressin. Although the incorporation of [32P]Pi into hepatocyte lipids was decreased when cells were incubated in a Ca2+-free medium, vasopressin still provoked a substantial stimulation of phosphatidylinositol labelling under these conditions. Studies with the antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),8-arginine]vasopressin indicated that the hepatic vasopressin receptors that control phosphatidylinositol metabolism are similar to those that mediate the vasopressor response in vivo. When prelabelled hepatocytes were stimulated for 5 min and then subjected to subcellular fractionation. The decrease in [3H]phosphatidylinositol content in each cell fraction with approximately in proportion to its original phosphatidylinositol content. This may be a consequence of phosphatidylinositol breakdown at a single site, followed by rapid phosphatidylinositol exchange between membranes leading to re-establishment of an equilibrium distribution.

scholarly journals Stimulatory effect of the intestinal peptide PHI on glycogenolysis and gluconeogenesis in isolated rat hepatocytes

1983 ◽  
Vol 214 (3) ◽  
pp. 999-1002 ◽  
Author(s):  
J E Felíu ◽  
J Marco
Keyword(s):  
Cyclic Amp ◽  
Pyruvate Kinase ◽  
Glycogen Phosphorylase ◽  
Rat Hepatocytes ◽  
Fold Increase ◽  
Isolated Rat Hepatocytes ◽  
Mediated Effects ◽  
Dose Dependent ◽  
Isolated Rat ◽  
Stimulation Of

The newly isolated peptide PHI provoked a dose-dependent stimulation of glycogenolysis and gluconeogenesis in isolated rat hepatocytes; at 1 microM-PHI, both processes were increased 1.6-fold as compared with basal values. These PHI-mediated effects were accompanied by the activation of glycogen phosphorylase and the inactivation of pyruvate kinase. PHI (1 microM) also caused a 2-fold increase in hepatocyte cyclic AMP.

scholarly journals Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes

1987 ◽  
Vol 248 (2) ◽  
pp. 429-437 ◽  
Author(s):  
A Lavoinne ◽  
A Baquet ◽  
L Hue
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Diabetic Rats ◽  
Purine Analogues ◽  
Isolated Rat Hepatocytes ◽  
Body Production ◽  
Stimulation Of

Glutamine stimulated glycogen synthesis and lactate production in hepatocytes from overnight-fasted normal and diabetic rats. The effect, which was half-maximal with about 3 mM-glutamine, depended on glucose concentration and was maximal below 10 mM-glucose. beta-2-Aminobicyclo[2.2.1.]heptane-2-carboxylic acid, an analogue of leucine, stimulated glutaminase flux, but inhibited the stimulation of glycogen synthesis by glutamine. Various purine analogues and inhibitors of purine synthesis were found to inhibit glycogen synthesis from glucose, but they did not abolish the stimulatory effect of glutamine on glycogen synthesis. The correlation between the rate of glycogen synthesis and synthase activity suggested that the stimulation of glycogen synthesis by glutamine depended solely on the activation of glycogen synthase. This activation of synthase was not due to a change in total synthase, nor was it caused by a faster inactivation of glycogen phosphorylase, as was the case after glucose. It could, however, result from a stimulation of synthase phosphatase, since, after the addition of 1 nM-glucagon or 10 nM-vasopressin, glutamine did not interfere with the inactivation of synthase, but did promote its subsequent re-activation. Glutamine was also found to inhibit ketone-body production and to stimulate lipogenesis.

scholarly journals Stimulation of inorganic-phosphate incorporation into phosphatidylinositol in rat thoracic aorta mediated through V1-vasopressin receptors

1981 ◽  
Vol 194 (1) ◽  
pp. 167-172 ◽  
Author(s):  
A P Takhar ◽  
C J Kirk
Keyword(s):  
Thoracic Aorta ◽  
Rat Hepatocytes ◽  
Rat Aorta ◽  
Vasopressin Receptors ◽  
Rat Thoracic Aorta ◽  
Relative Potencies ◽  
Phosphate Incorporation ◽  
Vasopressin Analogues ◽  
Stimulation Of

Vasopressin stimulates the incorporation of [32P]Pi into phosphatidylinositol but not into other phospholipids in rat thoracic aorta strips. The relative abilities of three vasopressin analogues to stimulate phosphatidylinositol labelling in rat aorta are similar to their relative pressor potencies in vivo and to their relative potencies in stimulating the metabolism of rat hepatocytes, but very different from their relative antidiuretic potencies. The vasopressor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),8-arginine]vasopressin competitively inhibits [Arg8]vasopressin-stimulated phosphatidylinositol labelling in rat aorta with a pA2 of 8.1. It is concluded that the Ca2+-mobilizing vasopressin receptors (V1-receptors) of the rat aorta stimulate phosphatidylinositol metabolism, probably by enhancing phosphatidylinositol breakdown.

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 Comparative metabolism of the antiviral dimer 3'-azido-3'-deoxythymidine-P-2',3'-dideoxyinosine and the monomers zidovudine and didanosine by rat, monkey, and human hepatocytes.

1997 ◽  
Vol 41 (11) ◽  
pp. 2502-2510 ◽  
Author(s):  
X R Pan-Zhou ◽  
E Cretton-Scott ◽  
X J Zhou ◽  
M Y Xie ◽  
R Rahmani ◽  
...  
Keyword(s):  
High Performance ◽  
Rat Hepatocytes ◽  
Human Hepatocytes ◽  
Metabolic Fate ◽  
Extracellular Medium ◽  
Isolated Rat Hepatocytes ◽  
Cell Extracts ◽  
Comparative Metabolism ◽  
Isolated Rat

AZT-P-ddI is an antiviral heterodimer composed of one molecule of 3'-azido-3'-deoxythymidine (AZT) and one molecule of 2',3'-dideoxyinosine (ddI) linked through their 5' positions by a phosphate bond. The metabolic fate of the dimer was studied with isolated rat, monkey, and human hepatocytes and was compared with that of its component monomers AZT and ddI. Upon incubation of double-labeled [14C]AZT-P-[3H]ddI in freshly isolated rat hepatocytes in suspension at a final concentration of 10 microM, the dimer was taken up intact by cells and then rapidly cleaved to AZT, AZT monophosphate, ddI, and ddI monophosphate. AZT and ddI so formed were then subject to their respective catabolisms. High-performance liquid chromatography analyses of the extracellular medium and cell extracts revealed the presence of unchanged dimer, AZT, 3'-azido-3'-deoxy-5'-beta-D-glucopyranosylthymidine (GAZT), 3'-amino-3'-deoxythymidine (AMT), ddI, and a previously unrecognized derivative of the dideoxyribose moiety of ddI, designated ddI-M. Trace extracellular but substantial intracellular levels of the glucuronide derivative of AMT (3'-amino-3'-deoxy-5'-beta-D-glucopyranosylthymidine [GAMT]) were also detected. Moreover, the extent of the formation of AMT, GAZT, and ddI-M from the dimer was markedly lower than that with AZT and ddI alone by the hepatocytes. With hepatocytes in primary culture obtained from rat, monkey, and human, large interspecies variations in the metabolism of AZT-P-ddI were observed. While GAZT and ddI-M, metabolites of AZT and ddI, respectively, as well as AZT 5'-monophosphate (MP) and ddI-MP were detected in the extracellular media of all species, AMT and GAMT were produced only by rat and monkey hepatocytes. No such metabolites were formed by human hepatocytes. The metabolic fate of the dimer by human hepatocytes was consistent with in vivo data recently obtained from human immunodeficiency virus-infected patients.

Hepatic and extrahepatic factors critical for liver injury during lipopolysaccharide exposure

2001 ◽  
Vol 281 (6) ◽  
pp. G1423-G1431 ◽  
Author(s):  
Frederic Moulin ◽  
Bryan L. Copple ◽  
Patricia E. Ganey ◽  
Robert A. Roth
Keyword(s):  
Liver Injury ◽  
Polymorphonuclear Leukocytes ◽  
Rat Hepatocytes ◽  
Hepatocellular Injury ◽  
In Vitro Perfusion ◽  
Isolated Rat Hepatocytes ◽  
Hepatocellular Damage ◽  
Alt Activity

Bacterial endotoxin [lipopolysaccharide (LPS)] causes liver injury in vivo that is dependent on platelets, neutrophils [polymorphonuclear leukocytes (PMNs)], and several inflammatory mediators, including thrombin. We tested the hypothesis that thrombin contributes to LPS-induced hepatocellular injury through direct interactions with platelets and/or PMNs in vitro. Perfusion of isolated livers from LPS-treated rats with buffer containing thrombin resulted in a significant increase in alanine aminotransferase (ALT) activity in the perfusion medium, indicating hepatocellular damage. This effect was completely abolished by prior depletion of PMNs from the LPS-treated donor rats but not by depletion of platelets, suggesting interaction between thrombin and PMNs in the pathogenesis. Thrombin did not, however, enhance degranulation of rat PMNs in vitro, and it was not directly toxic to isolated rat hepatocytes in the presence of PMNs even after LPS exposure, suggesting that hepatocellular killing by the PMN-thrombin combination requires the intervention of an additional factor(s) within the liver. In livers from naive donors perfused with buffer containing PMNs and LPS, no injury occurred in the absence of thrombin. Addition of thrombin (10 nM) to the medium caused pronounced ALT release. These results indicate that thrombin and PMNs are sufficient extrahepatic requirements for LPS-induced hepatocellular damage in intact liver.

Sign in / Sign up

Export Citation Format

Share Document