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.

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.

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.

Selective plasmalogen substrate utilization by thrombin-stimulated Ca2+-independent PLA2in cardiomyocytes

2000 ◽  
Vol 278 (6) ◽  
pp. H1933-H1940 ◽  
Author(s):  
Jane McHowat ◽  
Michael H. Creer
Keyword(s):  
Arachidonic Acid ◽  
Ventricular Myocytes ◽  
Platelet Activating Factor ◽  
Substrate Utilization ◽  
Phospholipase A ◽  
Concomitant Change ◽  
Choline Phospholipid ◽  
Rabbit Ventricular Myocytes ◽  
Stimulation Of

Thrombin stimulation of rabbit ventricular myocytes activates a membrane-associated, Ca2+-independent phospholipase A2(PLA2) capable of hydrolyzing plasmenylcholine (choline plasmalogen), plasmanylcholine (alkylacyl choline phospholipid), and phosphatidylcholine substrates. To identify the endogenous phospholipid substrates, we quantified the effects of thrombin stimulation on diradyl phospholipid mass and arachidonic acid and lysophospholipid production. Thrombin stimulation resulted in a selective decrease in arachidonylated plasmenylcholine, with no change in arachidonylated phosphatidylcholine. The decrease in arachidonylated plasmenylcholine was accompanied by an increase in plasmenylcholine species containing linoleic and linolenic acids at the sn-2 position. A decrease in arachidonylated plasmenylethanolamine was also observed after thrombin stimulation, with no concomitant change in arachidonylated phosphatidylethanolamine. Thrombin stimulation resulted in the selective production of lysoplasmenylcholine, with no increase in lysophosphatidylcholine content. There was no evidence for significant acetylation of lysophospholipids to form platelet-activating factor. Arachidonic acid released after thrombin stimulation was rapidly oxidized to prostacyclin. Thus thrombin-stimulated Ca2+-independent PLA2selectively hydrolyzes arachidonylated plasmalogen substrates, resulting in production of lysoplasmalogens and prostacyclin as the principal bioactive products.

Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

1989 ◽  
Vol 257 (6) ◽  
pp. L373-L378 ◽  
Author(s):  
T. Sasaki ◽  
S. Shimura ◽  
K. Ikeda ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Platelet Activating Factor ◽  
Thromboxane A2 ◽  
Submucosal Gland ◽  
Thromboxane Receptor ◽  
Significant Stimulation ◽  
Submucosal Glands ◽  
Dose Dependent Fashion ◽  
Thromboxane Receptor Antagonist ◽  
Dose Dependent ◽  
Thromboxane A2 Analogue

Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation.

RELAXATIONS INDUCED BY LIPOXYGENASE METABOLITES OF ARACHI-DONIC ACID IN SPLENIC ARTERIES OF THE DOG

1987 ◽  
Author(s):  
M J Van Diest ◽  
T J Verbeuren ◽  
A G Herman
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin F2α ◽  
Thromboxane A2 ◽  
Ringer Solution ◽  
Isometric Tension ◽  
Hydroxy Derivative ◽  
Prostaglandin Receptors ◽  
Independent Mechanism ◽  
Txa2 Receptor ◽  
Hydroperoxyeicosatetraenoic Acid

The lipoxygenase metabolites of arachidonic acid, 15 hydroperoxyeicosatetraenoic acid (15HPETE) and its hydroxy derivative (15HETE) evoke contractions in a variety of isolated blood vessels. We recently were able to show that thromboxane A2 (TXA2)-receptor antagonists BM13177 and BM13505 suppress the contractions induced by lipoxygenase metabolites in canine splenic arteries, and that these compounds also inhibit the contractile effects of PGF2α and of the TXA2-mimetic U46619. We also reported that 15HETE and 15HPETE cause relaxations of isolated dog arteries when the tissues are contracted with prostaglandin F2α (PGF2α) or with U46619 and suggested that lipoxygenase metabolites may act as endogenous antagonists towards prostaglandin receptors. The present study was designed to investigate the effects of lipoxygenase metabolites of arachidonic acid in isolated splenic arteries in which the tone is raised by various agonists.Segments of canine splenic arteries with or without endothelium were placed in organ chambers filled with Krebs-Ringer solution at 37°C for isometric tension recording. Responses to 15HPETE were obtained in segments which were contracted with serotonin, K+, PGF2α or noradrenaline (the latter with or without BM13505); concentrations causing comparable levels of contraction were selected. HPETE evoked relaxations in segments with and without endothelium, during the contractions evoked by K+, PGF2α and noradrenaline (with or without BM13505). At higher concentrations, 15HPETE caused relaxations only during contractions induced by PGF2α and noradrenaline with BM13505. Our results suggest that 15HPETE can cause relaxations by two different mechanisms :(1) 15HPETE may act as an antagonist to PGF2α, which causes its contraction via the TXA2-receptor and,(2) in presence of BM13505, it suppresses the contractions to noradrenaline via an endothelium independent mechanism.

scholarly journals Activation of group VI phospholipase A2 isoforms in cardiac endothelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. C872-C879 ◽  
Author(s):  
Janhavi Sharma ◽  
John Turk ◽  
David J. Mancuso ◽  
Harold F. Sims ◽  
Richard W. Gross ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Platelet Activating Factor ◽  
Selective Inhibition ◽  
Wild Type ◽  
Human Coronary Artery ◽  
Group Vi ◽  
Bromoenol Lactone ◽  
Protease Activated Receptor 1 ◽  
Stimulation Of

The endothelium comprises a cellular barrier between the circulation and tissues. We have previously shown that activation of protease-activated receptor 1 (PAR-1) and PAR-2 on the surface of human coronary artery endothelial cells by tryptase or thrombin increases group VIA phospholipase A2 (iPLA2β) activity and results in production of multiple phospholipid-derived inflammatory metabolites. We isolated cardiac endothelial cells from hearts of iPLA2β-knockout (iPLA2β-KO) and wild-type (WT) mice and measured arachidonic acid (AA), prostaglandin I2 (PGI2), and platelet-activating factor (PAF) production in response to PAR stimulation. Thrombin (0.1 IU/ml) or tryptase (20 ng/ml) stimulation of WT endothelial cells rapidly increased AA and PGI2 release and increased PAF production. Selective inhibition of iPLA2β with ( S)-bromoenol lactone (5 μM, 10 min) completely inhibited thrombin- and tryptase-stimulated responses. Thrombin or tryptase stimulation of iPLA2β-KO endothelial cells did not result in significant PAF production and inhibited AA and PGI2 release. Stimulation of cardiac endothelial cells from group VIB (iPLA2γ)-KO mice increased PAF production to levels similar to those of WT cells but significantly attenuated PGI2 release. These results indicate that cardiac endothelial cell PAF production is dependent on iPLA2β activation and that both iPLA2β and iPLA2γ may be involved in PGI2 release.

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