Possible involvement of eicosanoids in the actions of sympathetic hepatic nerves on carbohydrate metabolism and hemodynamics in perfused rat liver

Iwai, Masaru; Jungermann, Kurt

doi:10.1016/0014-5793(87)80371-x

Cited by 54 publications

(25 citation statements)

References 34 publications

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“…san [ l I], endotoxins [12], heat-aggregated immunoglobulins [13], peptides of the activated complement system [14-161, platelet-activating factor [ 171, extracellular nucleotides and nucleosides [18,191, phorbol esters [20,211 and stimulation of sympathetic hepatic nerves [22]. Many of these effectors have also been shown to stimulate eicosanoid formation in Kupffer cells.…”

mentioning

confidence: 99%

Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways

Püschel

Kirchner

Schröder

et al. 1993

European Journal of Biochemistry

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Prostaglandin E, has been reported both to stimulate glycogen-phosphorylase activity (glycogenolytic effect) and to inhibit the glucagon-stimulated glycogen-phosphorylase activity (antiglycogenolytic effect) in rat hepatocytes. It was the purpose of this study to resolve this apparent contradiction and to characterize the signalling pathways and receptor subtypes involved in the opposing prostaglandin E, actions.Prostaglandin E, (10 pM) increased glucose output, glycogen-phosphorylase activity and inositol trisphosphate formation in hepatocyte cell culture andor suspension. In the same systems, prostaglandin E, decreased the glucagon-stimulated (1 nM) glycogen-phosphorylase activity and cAMP formation.The signalling pathway leading to the glycogenolytic effect of PGE, was interrupted by incubation of the hepatocytes with 4P-phorbol 12-myristate 13-acetate (100 nM) for 10 min, while the antiglycogenolytic effect of prostaglandin E, was not attenuated.The signalling pathway leading to the antiglycogenolytic effect of prostaglandin E, was interrupted by an incubation of cultured hepatocytes with pertussis toxin (100 ng/ml) for 18 h, whereas the glycogenolytic effect of prostaglandin E, was enhanced.The EP,/EP, prostaglandin-E,-receptor-specific prostaglandin E, analogue Sulproston had a stronger glycogenolytic potency than the EP, prostaglandin-E,-receptor-specific prostaglandin E, analogue Misoprostol. The antiglycogenolytic potency of both agonists was equal.It is concluded that the glycogenolytic and the antiglycogenolytic effects of prostaglandin E, are mediated via different signalling pathways in hepatocytes possibly involving EP, and EP, prostaglandin E, receptors, respectively.Prostaglandins have been implicated to participate in cell to cell signal propagation between non-parenchymal and parenchymal cells in the liver. They are synthesized only in non-parenchymal liver cells [ 11, primarily Kupffer cells, but also in endothelial cells and Ito cells. They are degraded mainly by the parenchymal cells, i.e. hepatocytes [2-61, which also have been shown to possess binding sites for prostaglandins [2,[7][8][9][10]. The role of prostaglandins in the regulation of liver metabolism has been discussed controversially in previous studies. The use of cyclooxygenase inhibitors have revealed the involvement of prostaglandins in signalling pathways leading to an increase in glycogenolysis and glucose output elicited by such diverse stimuli as zymoCorrespondence to G. P.

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mentioning

confidence: 99%

Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways

Püschel

Kirchner

Schröder

et al. 1993

European Journal of Biochemistry

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“…The mechanism of nerve action is more complex than an interaction of two hormones. Probably, the nerve effects are mediated by interactions of the nerve endings of the neurons, the non-parenchymal cells and parenchymal cells [13,24]. The presynaptic site of action was excluded by the determination of the unaltered overflow of noradrenaline.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was shown that inhibitors of the synthesis of prostanoids reduced the nerve-mediated effects [13]. Prostaglandins were reported to be released after nerve stimulation [25].…”

Section: Discussionmentioning

confidence: 99%

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Modulation by somatostatin of nerve‐mediated activation of glycogenolysis in the perfused rat liver

Beckh¹,

Eder²,

Arnold³

1989

FEBS Letters

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Perivascular nerve stimulation of rat livers perfused in situ with erythrocyte-free Krebs-Henseleit buffer at constant pressure in a non-reci/'culating system resulted in an increase of glucose and lactate production and in a decrease of portal flow. Infusion of somatostatin in different concentrations (2 x 10 '7, 10 -8, 10 -9 mol.1-1 ) reduced the nerve-mediated activation of glucose releasemaximally to 66%. There was only a slight effect on the lactate output, the nerve-mediated reduction of portal flow was unaltered. In controls, somatostatin alone had no effect on the metabolic and hemodynamic parameters. In order to differentiate between a presynaptic and postsynaptic mechanism, the noradrenaline overflow was calculated. The unaltered release of the neurotransmitter in the presence or absence of somatostatin excluded a presynaptic mechanism. To mimic the nerve effects on the carbohydrate metabolism and on the hemodynamics, noradrenaline (2 x 10 -7. mol-1-1) was infused instead of the nerve stimulation over a period of 5 min. Somatostatin did not change the endocrine effects of the eatecholamine under these conditions. The nerve-dependent effect of somatostatin suggests that other neurotransmitters (e.g. VIP) or mediators (e.g. prostanoids) may be influenced by somatostatin.

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“…Recently evidence has been obtained that eicosanoids, which are synthesized only in non-parenchymal liver cells, mainly endothelial and Kupffer cells [61], might be involved as mediators and/or modulators of sympathetic nerve action on both hepatic metabolism and hemodynamics [62]. Since eicosanoid formation requires the liberation of arachidonate from endogenous phospholipids [61] by calcium-activated phospholipase A2 [63], the possibility has to be considered that intracellular calcium plays a role in the metabolic nerve action not only in the hepatocytes proper but also in the non-parenchymal liver cells.…”

Section: Calciummentioning

confidence: 99%

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

Balle¹,

Beuers²,

Engelhardt³

et al. 1987

European Journal of Biochemistry

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In rat liver perfused in situ stimulation of the nerve plexus around the hepatic artery and the portal vein caused an increase in glucose output and a shift from lactate uptake to output. The effects of nerve stimulation on some key enzymes, metabolites and effectors of carbohydrate metabolism were determined and compared to the actions of glucagon, which led to an increase not only of glucose output but also of lactate uptake.1. Nerve stimulation caused an enhancement of the activity of glycogen phosphorylase a to 300% and a decrease of the activity of glycogen synthase I to 40%, while it left the activity of pyruvate kinase unaltered. Glucagon, similarly to nerve action, led to a strong increase of glycogen phosphorylase and to a decrease of glycogen synthase; yet in contrast to the nerve effect it lowered pyruvate kinase activity clearly.2. Nerve stimulation increased the levels of glucose 6-phosphate and of fructose 6-phosphate to 200% and 170%, respectively; glucagon enhanced the levels to about 400% and 230%, respectively. The levels of ATP and ADP were not altered, those of AMP were increased slightly by nerve stimulation. 3.Nerve stimulation enhanced the levels of the effectors fructose 2,6-bisphosphate and cyclic AMP only slightly to 140% and 125%, respectively; glucagon lowered the level of fructose 2,6-bisphosphate to 15% and increased the level of cyclic AMP to 300%.4. In calcium-free perfusions the metabolic responses to nerve stimulation showed normal kinetics, if calcium was re-added 3 min before, but delayed kinetics, if it was re-added 2 min after the onset of the stimulus. The delay may be due to the time required to refill intracellular calcium stores. The hemodynamic alterations dependent on extracellular calcium were normal in both cases.The activation of glycogen phosphorylase, the inhibition of glycogen synthase and the increase of glucose 6-phosphate can well explain the enhancement of glucose output following nerve stimulation. The unaltered activity of pyruvate kinase and the marginal increase of fructose 2,6-bisphosphate cannot be the cause of the nervestimulation-dependent shift from lactate uptake to output. The very slight increase of the level of cyclic AMP after nerve stimulation cannot elicit the observed activation of glycogen phosphorylase. This finding and the delayed metabolic response of calcium-depleted/repleted livers to nerve stimulation suggest that activation of the enzyme after nerve stimulation is mediated by an increase of cytosolic calcium, which would be in accord with the observed a-mechanism.

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Possible involvement of eicosanoids in the actions of sympathetic hepatic nerves on carbohydrate metabolism and hemodynamics in perfused rat liver

Cited by 54 publications

References 34 publications

Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways

Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways

Modulation by somatostatin of nerve‐mediated activation of glycogenolysis in the perfused rat liver

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

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Possible involvement of eicosanoids in the actions of sympathetic hepatic nerves on carbohydrate metabolism and hemodynamics in perfused rat liver

Cited by 54 publications

References 34 publications

Glycogenolytic and antiglycogenolytic prostaglandin E2 actions in rat hepatocytes are mediated via different signalling pathways

Glycogenolytic and antiglycogenolytic prostaglandin E2 actions in rat hepatocytes are mediated via different signalling pathways

Modulation by somatostatin of nerve‐mediated activation of glycogenolysis in the perfused rat liver

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

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Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways

Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways