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 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 Evidence from studies employing radioactively labelled fatty acids that the stimulation of flux through the diacylglycerol pool is an early action of vasopressin on hepatocytes

1987 ◽  
Vol 245 (1) ◽  
pp. 211-216 ◽  
Author(s):  
L B Pickford ◽  
A J Polverino ◽  
G J Barritt
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Phosphatidic Acid ◽  
Isolated Hepatocytes ◽  
Maximal Increase ◽  
Maximal Stimulation ◽  
Early Action ◽  
Palmitic Acids ◽  
Stimulation Of ◽  
In Cells

1. In isolated hepatocytes prelabelled with [14C]-arachidonic, -stearic, -linoleic, -oleic or -palmitic acids, vasopressin increased the amount of radioactivity present in diacylglycerols. The largest increase was observed in cells labelled with arachidonic or stearic acids. 2. In cells prelabelled with [14C]- or [3H]-arachidonic acid, the onset of the increase in radioactivity in diacylglycerols induced by vasopressin was slow, the increase was partly dependent on the presence of extracellular Ca2+, and was associated with an increase in radioactivity present in phosphatidic acid which was more rapid in onset. Vasopressin decreased the amount of [3H]arachidonyl-phosphatidylinositol 4,5-bisphosphate, but the magnitude of this decrease was less than 10% of the observed increase in radioactivity in [3H]arachidonyl-diacylglycerol. 3. The concentration of vasopressin which gave half-maximal increase in [14C]arachidonyl-diacylglycerol at low extracellular Ca2+ was 10-fold higher than that which gave half-maximal stimulation of 45Ca2+ efflux. Phenylephrine, but not glucagon, also increased the amount of [14C]arachidonyl-diacylglycerol. 4. It is concluded that an early action of vasopressin on the liver cell is to increase the flux of carbon from phospholipids, including the phosphoinositides, to diacylglycerols.

Microbubble-Induced Phospholipase C Activation Does not Correlate with Platelet Aggregation

1993 ◽  
Vol 69 (04) ◽  
pp. 394-396 ◽  
Author(s):  
R Malmgren ◽  
T Thorsen ◽  
A Nordvik ◽  
H Holmsen
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Phosphatidic Acid ◽  
Phospholipase C ◽  
Human Platelets ◽  
Similar Extent ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Rule Out ◽  
Stimulation Of

SummaryThe effect of nitrogen-(N2-)microbubbles on platelets resembles that of common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This paper reports the effect of microbubbles on platelet phospholipase C activity in gelfiltered human platelets prelabelled with [32P]Pi ([32P]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADP. Stimulation of [32P]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p <0.0004) and a significant increase in 32P-activity in the phosphatidic acid (PA) fraction (p <0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p <0.05), but did not enhance the amount of 32P in the platelet [32P]PA fraction. The 32P-radioactivity in the PI-fraction increased with time to a similar extent when [32P]-GFP was stirred for 30 min in absence of microbubbles as it did after 30 min of agonist exposure. There were no significant changes in the [32P]PIP and [32P]PIP2 fractions. Aspirin abolished the microbubble-induced increase in 32P-activity in the PA fraction, but had no significant effect on the reduction in single platelets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles (p <0.05). With epinephrine, however, aspirin did not completely abolish the increase in [32P]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates independent of cyclooxygenase-dependent arachidonic acid metabolites and phospholipase C activation.

scholarly journals The Ca2+-mobilizing actions of vasopressin and angiotensin differ from those of the α-adrenergic agonist phenylephrine in the perfused rat liver

1985 ◽  
Vol 232 (3) ◽  
pp. 911-917 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Similar Amount ◽  
Perfused Rat Liver ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Hormone Administration ◽  
Sensitive Electrode ◽  
Stimulation Of

A Ca2+-sensitive electrode was used to study net Ca2+-flux changes induced by the administration of phenylephrine, vasopressin and angiotensin to the perfused rat liver. The studies reveal that, although the Ca2+ responses induced by vasopressin and angiotensin are similar, they are quite different from the Ca2+ fluxes induced by phenylephrine. The administration of phenylephrine is accompanied by a stimulation of a net amount of Ca2+ efflux (140 nmol/g of liver). A re-uptake of a similar amount of Ca2+ occurs only after the hormone is removed. In contrast, the administration of vasopressin or angiotensin to livers perfused with 1.3 mM-Ca2+ induces the release of a relatively small amount of Ca2+ (approx. 40 nmol/g of liver) during the first 60 s. This is followed by a much larger amount of Ca2+ uptake (70-140 nmol/g of liver) after 1-2.5 min of hormone administration, and a slow efflux or loss of a similar amount of Ca2+ over a period of 6-8 min. At lower concentrations of perfusate Ca2+ (less than 600 microM) these hormones induce only a net efflux of the ion. These results suggest that at physiological concentrations of extracellular Ca2+ the mechanism by which alpha-adrenergic agonists mobilize cellular Ca2+ is different from that involving vasopressin and angiotensin. It seems that the hormones may have quite diverse effects on Ca2+ transport across the plasma membrane and perhaps organellar membranes in liver.

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.

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.

Subacinar distribution of hepatocyte membrane potential response to stimulation of gluconeogenesis

1992 ◽  
Vol 263 (3) ◽  
pp. G319-G326 ◽  
Author(s):  
S. M. Lee ◽  
M. G. Clemens
Keyword(s):  
Membrane Potential ◽  
Cell Communication ◽  
Membrane Potentials ◽  
Differential Modulation ◽  
O2 Uptake ◽  
Retrograde Perfusion ◽  
Exogenous Substrate ◽  
Hormone Effects ◽  
Rat Livers ◽  
Stimulation Of

Isolated rat livers were perfused and the membrane potentials of matched periportal and pericentral hepatocytes were determined using glass microelectrodes. O2 uptake and gluconeogenesis were increased by both phenylephrine and glucagon and the extent of the increase was not affected by the direction of perfusion. With no exogenous substrate, hepatocyte membrane potentials were approximately -27 mV. No gradients were found. Substrate produced hyperpolarization in all hepatocytes, with a small but significant gradient produced. Phenylephrine-induced hyperpolarization was higher in periportal than in pericentral hepatocytes during anterograde perfusion, but reversed during retrograde perfusion. Similar effects on membrane potential were produced by phorbol myristate acetate (PMA). Glucagon hyperpolarized homogeneously during both anterograde and retrograde perfusion with no gradients across the acinus. Octanol addition during glucagon stimulation, however, resulted in heterogeneity similar to phenylephrine or PMA. Thus when hepatocytes are stimulated by substrate or hormones, the degree of hepatocyte membrane potential heterogeneity across the acinus is highly dependent on the nature of the stimulus. We propose that the differential hormone effects on hepatocyte membrane potential may be mediated at least in part by differential modulation of cell to cell communication via gap junctions.

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