scholarly journals Evidence that Ca2+ fluxes and respiratory, glycogenolytic and vasoconstrictive effects induced by the action of platelet-activating factor and l-α-lysophosphatidylcholine in the perfused rat liver are mediated by products of the cyclo-oxygenase pathway

1987 ◽  
Vol 245 (1) ◽  
pp. 145-150 ◽  
Author(s):  
J G Altin ◽  
P Dieter ◽  
F L Bygrave
Keyword(s):  
Maximum Rate ◽  
Physiological Responses ◽  
Portal Pressure ◽  
Platelet Activating Factor ◽  
Cell Types ◽  
Maximal Response ◽  
Perfused Rat Liver ◽  
Glucose Output ◽  
Rat Livers ◽  
By Products

The administration of ‘acetylglyceryl ether phosphorylcholine’ (AGEPC, also known as platelet-activating factor) and L-alpha-lysophosphatidylcholine (LPC) to rat livers perfused with media containing 1.3 mM-Ca2+ was followed by a concentration-dependent efflux of Ca2+ from the liver. Near-maximal response was observed at 100 nM-AGEPC and 50 microM-LPC, and resulted in a net efflux of approx. 130 nmol of Ca2+/g of liver. Onset of Ca2+ efflux occurred about 10 s after AGEPC and LPC administration, reached a maximum after about 50 s (the maximum rate of efflux was approx. 180 nmol/min per g) and thereafter decreased rapidly, and was sometimes followed by a much smaller influx of Ca2+. Sequential infusions of AGEPC or LPC, and phenylephrine, indicate that each of these agents mobilizes Ca2+ from the same intracellular source. The efflux of Ca2+ was not observed in the presence of indomethacin or bromophenacyl bromide, or when the liver was perfused with low-Ca2+-containing (25 microM) media. Other physiological responses, such as changes in respiration, glucose output and portal pressure, were also inhibited under these conditions. The results suggest that the Ca2+-flux changes and other responses are mediated by prostaglandins produced and released within the liver, possibly by cell types other than hepatocytes.

scholarly journals Phosphatidic acid and arachidonic acid each interact synergistically with glucagon to stimulate Ca2+ influx in the perfused rat liver

1987 ◽  
Vol 247 (3) ◽  
pp. 613-619 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave
Keyword(s):  
Arachidonic Acid ◽  
Phosphatidic Acid ◽  
Synergistic Action ◽  
Perfused Rat Liver ◽  
O2 Uptake ◽  
Adrenergic Agonist ◽  
Glucose Output ◽  
Rat Livers ◽  
Alpha Adrenergic Agonist ◽  
Stimulation Of

The administration of phosphatidic acid to rat livers perfused with media containing either 1.3 mM- or 10 microM-Ca2+ was followed by a stimulation of Ca2+ efflux, O2 uptake and glucose output. The responses elicited by 100 microM-phosphatidic acid were similar to those induced by the alpha-adrenergic agonist phenylephrine. Contrary to suggestions that phosphatidic acid acts like a Ca2+-ionophore, no net influx of Ca2+ was detected until the phosphatidic acid was removed. Sequential infusions of phenylephrine and phosphatidic acid indicate that the two agents release Ca2+ from the same intracellular source. The co-administration of glucagon (or cyclic AMP) and phosphatidic acid, and also of glucagon and arachidonic acid, led to a synergistic stimulation of Ca2+ uptake of the liver, a feature similar to that observed after the co-administration of glucagon and other Ca2+-mobilizing hormones [Altin & Bygrave (1986) Biochem. J. 238, 653-661]. A notable difference, however, is that the synergistic stimulation of Ca2+ uptake induced by the co-administration of glucagon and arachidonic acid was inhibited by indomethacin, whereas that induced by glucagon and phosphatidic acid, or glucagon and other Ca2+-mobilizing agents, was not. The results suggest that the synergistic action of glucagon and arachidonic acid in stimulating Ca2+ influx is mediated by prostanoids, but that of glucagon and phosphatidic acid is evoked by a mechanism similar to that of Ca2+-mobilizing agents.

The Effect of Combined Ischaemia and Acidosis on Lactate Uptake and Gluconeogenesis in the Perfused Rat Liver

1981 ◽  
Vol 60 (5) ◽  
pp. 537-542 ◽  
Author(s):  
R. A. Iles ◽  
R. D. Cohen ◽  
P. G. Baron
Keyword(s):  
Lactic Acid ◽  
Rat Liver ◽  
Hepatic Uptake ◽  
Strenuous Exercise ◽  
Perfused Rat Liver ◽  
Lactate Uptake ◽  
Glucose Output ◽  
Rat Livers

1. Perfused rat livers were subjected to an acid perfusate and varying degrees of ischaemia in an attempt to simulate the conditions of strenuous exercise or shock. 2. Lactate uptake and glucose output from the liver decreased during moderate ischaemia alone and more so when, in addition, the perfusate was made acidic. 3. Hepatic ATP and ADP content increased in the presence of an acid perfusate. 4. It is concluded that both ischaemia and acidosis may contribute to the diminished hepatic uptake of lactic acid in strenuous exercise and shock.

scholarly journals Stimulation of release of prostaglandin D2 and thromboxane B2 from perfused rat liver by extracellular adenosine

1990 ◽  
Vol 270 (1) ◽  
pp. 39-44 ◽  
Author(s):  
S vom Dahl ◽  
M Wettstein ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Rat Liver ◽  
Portal Pressure ◽  
Thromboxane B2 ◽  
Adenosine Infusion ◽  
Isolated Perfused Rat Liver ◽  
Signal Molecules ◽  
Prostaglandin D2 ◽  
Perfused Rat Liver ◽  
Glucose Output ◽  
Stimulation Of

In isolated perfused rat liver, adenosine infusion (50 microM) led to increases in glucose output and portal pressure and a net K+ release of 3.7 +/- 0.21 mumol/g, which was followed by an equivalent net K+ uptake after cessation of the nucleoside infusion. These effects were accompanied by a transient stimulation of hepatic prostaglandin D2 and thromboxane B2 release. The Ca2+ release observed upon adenosine infusion (50 microM) was 23.5 +/- 5.2 nmol/g, i.e. 10-20% of the Ca2+ release observed with extracellular ATP (50 microM). Indomethacin (10 microM) prevented the adenosine-induced stimulation of glucose output and the increase in portal pressure by 79 and 63% respectively, and completely abolished the stimulation of prostaglandin D2 release. The thromboxane A2 receptor antagonist BM 13.177 (20 microM), the phospholipase A2 inhibitor 4-bromophenacyl bromide (20 microM) and the cyclo-oxygenase inhibitor ibuprofen (50 microM) also decreased the glycogenolytic and vasoconstrictive responses of the perfused rat liver upon adenosine infusion by 50-80%. When the indomethacin inhibition of adenosine-induced prostaglandin D2 release was titrated, a close correlation between prostaglandin D2 release and the metabolic and vascular responses to adenosine was observed. These findings suggest an important role for eicosanoids in mediating the nucleoside responses in the perfused rat liver. Since eicosanoids are known to be formed by non-parenchymal cells in rat liver [Decker (1985) Semin. Liver Dis. 5, 175-190], the present study gives further evidence for an important role of eicosanoids as signal molecules between the different liver cell populations.

Regulation of hepatic glycogenolysis and vasoconstriction during antigen-induced anaphylaxis

1992 ◽  
Vol 262 (5) ◽  
pp. G868-G877 ◽  
Author(s):  
K. L. Hines ◽  
R. A. Fisher
Keyword(s):  
Blood Glucose Concentration ◽  
Portal Pressure ◽  
Platelet Activating Factor ◽  
Systemic Arterial Pressure ◽  
Venous Circulation ◽  
Hepatic Glucose ◽  
Paf Receptor ◽  
Hepatic Portal ◽  
Glucose Output ◽  
Web 2086

Effects of sensitizing antigen (ovalbumin) on various physiological and hepatic parameters were investigated in sensitized rats and isolated perfused livers derived from sensitized rats. Administration of ovalbumin (500 micrograms) to the portal venous circulation of sensitized but not nonsensitized rats resulted in a rapid and sustained decrease in systemic arterial pressure, characteristic of antigen-induced anaphylaxis, and pronounced increases in hepatic portal pressure and blood glucose concentration. These antigen-mediated alterations were similar to those observed in response to platelet-activating factor (PAF) (0.1 micrograms/kg) administration to rats and were inhibited significantly by specific PAF receptor antagonist WEB 2086 (250 micrograms/kg). Infusion of ovalbumin (3.8 micrograms/ml) into isolated perfused livers derived from sensitized rats resulted in significant increases in hepatic glucose output and portal pressure and decreases in oxygen consumption, as observed in response to PAF (0.28 nM) infusion into perfused livers. These hepatic responses to ovalbumin were antigen specific and were not observed in nonsensitized rat perfused livers. Hemodynamic and glycogenolytic responses to ovalbumin in perfused livers were inhibited significantly but less effectively than similar responses to PAF by infusion of WEB 2086 (500 nM) into livers. Coinfusion of indomethacin (2.8 microM) and nordihydroguariatic acid (1 microM) with WEB 2086 (500 nM) into perfused livers inhibited further hemodynamic but not glycogenolytic responses to ovalbumin. Infusion of nitric oxide (34 microM) into sensitized rat perfused livers prevented the hemodynamic and glycogenolytic responses to both ovalbumin and PAF. These observations provide evidence that hepatic glycogenolysis and vasoconstriction are stimulated during antigen-induced anaphylaxis and suggest that these responses are mediated in part by PAF.

scholarly journals Prostaglandin F2α and the thromboxane A2 analogue ONO-11113 stimulate Ca2+ fluxes and other physiological responses in rat liver. Further evidence that prostanoids may be involved in the action of arachidonic acid and platelet-activating factor

1988 ◽  
Vol 249 (3) ◽  
pp. 677-685 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave
Keyword(s):  
Arachidonic Acid ◽  
Portal Pressure ◽  
Platelet Activating Factor ◽  
Prostaglandin F2α ◽  
Thromboxane A2 ◽  
Prostaglandin D2 ◽  
O2 Uptake ◽  
Glucose Output ◽  
Thromboxane A2 Analogue ◽  
Stimulation Of

The administration of prostaglandin F2 alpha (PGF2 alpha) and the thromboxane A2 analogue, ONO-11113, to rat livers perfused with media containing either 1.3 mM- or 10 microM-Ca2+ was followed by a stimulation of Ca2+ efflux, changes in O2 uptake and glucose output, and increase in portal pressure. The responses elicited by 5 microM-PGF2 alpha were similar to those induced by the alpha-adrenergic agonist phenylephrine. At both 1.3 mM and 10 microM extracellular Ca2+, PGF2 alpha induced Ca2+ efflux (70-90 nmol/g of liver), probably from the same source as that released by phenylephrine. Prostaglandin D2 (5 microM) and prostaglandin E2 (5 microM) also induced responses, but these were generally much smaller (less than 30%) than those induced by PGF2 alpha. Similarly to vasopressin and other Ca2+-mobilizing hormones, PGF2 alpha also interacted synergistically with glucagon (and cyclic AMP) in stimulating Ca2+ influx both in the perfused liver and in isolated hepatocytes. By comparison with phenylephrine and PGF2 alpha, ONO-11113 was much more potent in inducing vasoconstriction, and, at concentrations of 10-200 nM, induced a different pattern of changes in Ca2+ flux, respiration and glycogenolysis. There was first a rapid efflux of Ca2+ (45-60 nmol/g of liver), followed by a smaller Ca2+ influx, and a further release of Ca2+ (approx. 90 nmol/g of liver) when ONO-11113 was removed. Respiration was first stimulated but then markedly inhibited. At concentrations less than 5 nM, ONO-11113 induced a sustained stimulation of O2 uptake and a more prolonged efflux of Ca2+, with less Ca2+ efflux occurring upon the removal of the agent. Glycogenolysis followed a pattern which was similar to the Ca2+ response. Co-administration of glucagon did not potentiate Ca2+ influx by ONO-11113, but the action of ONO-11113 was inhibited (50%) by a few minutes' prior administration of 10 nM-vasopressin. The vasoconstrictive action of ONO-11113 was synergistically potentiated by the co-administration of phenylephrine. Since the actions of arachidonic acid, platelet-activating factor and lysophosphatidylcholine in liver were recently found to be cyclo-oxygenase-sensitive, the results provide strong evidence that at least PGF2 alpha and thromboxane A2 may be involved in mediating the action of these agents.

A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver

1982 ◽  
Vol 47 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Yoav Sharoni ◽  
Maria C Topal ◽  
Patricia R Tuttle ◽  
Henry Berger
Keyword(s):  
Rat Liver ◽  
Isoelectric Point ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Plasminogen Activators ◽  
Rat Plasma ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Molecular Weights ◽  
Physiological Relevance

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.

scholarly journals Consumption of Enriched Yogurt with PAF Inhibitors from Olive Pomace Affects the Major Enzymes of PAF Metabolism: A Randomized, Double Blind, Three Arm Trial

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Lipid Mediator ◽  
Olive Pomace ◽  
Double Blind ◽  
Promising Alternative ◽  
Catabolic Enzymes ◽  
Platelet Activating Factor Acetylhydrolase ◽  
The Impact ◽  
By Products ◽  
Apparently Healthy

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

Vanadate inhibits glucose output from isolated perfused rat liver

Hepatology ◽  
1991 ◽  
Vol 14 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Rafael Bruck ◽  
Haia Prigozin ◽  
Zipora Krepel ◽  
Paul Rotenberg ◽  
Yoram Shechter ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Glucose Output

scholarly journals Activation and Regulation of Cellular Eicosanoid Biosynthesis

2007 ◽  
Vol 7 ◽  
pp. 1273-1284 ◽  
Author(s):  
Thomas G. Brock ◽  
Marc Peters-Golden
Keyword(s):  
Arachidonic Acid ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Inflammatory Responses ◽  
Physiological Responses ◽  
Cell Types ◽  
Key Points ◽  
Enzymatic Pathways

There is a growing appreciation for the wide variety of physiological responses that are regulated by lipid messengers. One particular group of lipid messengers, the eicosanoids, plays a central role in regulating immune and inflammatory responses in a receptor-mediated fashion. These mediators are related in that they are all derived from one polyunsaturated fatty acid, arachidonic acid. However, the various eicosanoids are synthesized by a wide variety of cell types by distinct enzymatic pathways, and have diverse roles in immunity and inflammation. In this review, the major pathways involved in the synthesis of eicosanoids, as well as key points of regulation, are presented.

Sign in / Sign up

Export Citation Format

Share Document