Modulation of maximal glycogenolysis in perfused rat liver by adenosine and ATP

Vanstapel, Florent; Waebens, M; Hecke, Paul Van; Decanniere, C.; Stalmans, Willy

doi:10.1042/bj2770597

Cited by 16 publications

(16 citation statements)

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“…Infusion is prone to be modulated (inter alia by changes in P i availability). 2,34 Such effects are readily recognized in of an equimolar concentration of NO 0 2 had no effect on hepatic glucose production (n Å 4; results not shown). livers in which phosphorylase is clamped fully in its active a-form, and changes in the rate of glycogenolysis NO (Fig.…”

Section: Camentioning

confidence: 92%

Modulation of basal hepatic glycogenolysis by nitric oxide

et al. 1996

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Glycogenolysis is catalysed by glycogen phosphorylactivation of phosphorylase. The NO effect was not addi-ase, an enzyme that exists in two interconvertible tive to maximal stimulation of glycogenolysis (7.7 { 0.2 forms, the active phosphorylated a-form and the inac- strictly depends on covalent activation of phosphoryl-The requirement for activation of phosphorylase was also evidenced by the ineffectiveness of NO in phosphor-ase, 1 by a specific phosphorylase kinase. The kinase is ylase-kinase-deficient livers of gsd/gsd rats. The NO activated by cyclic adenosine monophosphate (cAMP)-effect was blocked by co-administration of cyclooxy-dependent protein kinase, or by direct interaction of genase inhibitors (50 mmol/L ibuprofen, 50 mmol/L in-Ca 2/ with a calmodulin subunit. Ultimately, the catadomethacin, or 2 mmol/L aspirin), suggesting a media-lytic expression of phosphorylase a is under substrate tory role of prostanoids from nonparenchymal cells. control, 2 because cytosolic levels of inorganic phosphate This conclusion was confirmed by the fact that NO did (P i ) fail to saturate substrate demands of activated not activate phosphorylase in isolated hepatocytes. phosphorylase a. Moreover, NO was no longer glycogenolytic in liversControl of hepatic glycogenolysis involves intricate 3-7 Evidence has accumulated inhibited the basal glucose production. This coincided that prostanoids are engaged in the control of glycogenwith an increased elution of cyclic guanosine mono-olysis in liver. Although endotoxin, 8 platelet-activating phosphate (cGMP). Inhibition of glycogenolysis by NO factor, 9 and phorbol esters 3,8 stimulate glycogenolysis under these conditions was blocked by 1 mmol/L the-in intact liver, these compounds are ineffective when ophylline, suggestive for involvement of cGMP-stimu-tested directly on isolated hepatocytes. In the intact lated cAMP phosphodiesterase. However, we could not liver, cyclooxygenase inhibitors suppress stimulation confirm that an increase in cGMP resulted in a drop of prostanoid synthesis and activation of phosphorylase in cAMP. In conclusion, NO recruits opposing mechaby the former agents.10-12 Prostanoids may be directly involved in covalent activation of hepatocellular phosphorylase. 8,13 Indirectly, eicosanoids may trigger vaso- lytic response to platelet-activating factor is sup-

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Section: Camentioning

confidence: 92%

Modulation of basal hepatic glycogenolysis by nitric oxide

et al. 1996

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“…ATP and adenosine are known to affect the activity state of synthase and phosphorylase [4][5][6]11,15,32,[38][39][40]. Adenosine has been reported to activate adenylate cyclase in the livers from fed rats [4][5][6]32,33] whereas other groups failed to observe an increase in cyclic AMP in the presence of adenosine in livers of fasted rats [11,15].…”

Section: Role Of Atp and Cyclic Ampmentioning

confidence: 99%

“…This enzyme is responsible for the phosphorylation of adenosine to AMP within the cells. Itu has been used to distinguish between the effects of adenosine and its phosphorylated products [4]. Adenosine interacts with P1-receptors that activate adenylate cyclase, whereas ATP interacts with P2 -receptors and evokes a transient Ca2+-response [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Itu has been used to distinguish between the effects of adenosine and its phosphorylated products [4]. Adenosine interacts with P1-receptors that activate adenylate cyclase, whereas ATP interacts with P2 -receptors and evokes a transient Ca2+-response [4][5][6]. Itu alone has no effects on P1-or P2-receptors [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Adenosine interacts with P1-receptors that activate adenylate cyclase, whereas ATP interacts with P2 -receptors and evokes a transient Ca2+-response [4][5][6]. Itu alone has no effects on P1-or P2-receptors [3,4]. It has been reported that addition of Itu leads to an accumulation of adenosine in rat hepatocytes [1] and potentiates the action of exogenously added adenosine on heart rate, blood pressure and adenosine-stimulated cyclic AMP generation [3].…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of rat liver glycogen synthesis by the adenosine kinase inhibitor 5-iodotubercidin

Flückiger-Isler¹,

Walter²

1993

Biochemical Journal

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The adenosine kinase inhibitor 5-iodotubercidin (Itu) was found to have the following effects on glycogen metabolism in hepatocytes of fasted rats. (1) Itu strongly stimulated glycogen synthesis from different substrates (glucose, lactate plus pyruvate, dihydroxyacetone, glycerol and fructose). In cells incubated with these substrates, the well-known stimulating effect of amino acids and that of Itu was more than additive. (2) In parallel with the increase in glycogen deposition, there was an increase in synthase a and a decrease in phosphorylase a concentrations after administration of Itu. Synthase a was increased by Itu and amino acids in an additive manner, whereas the observed activation of phosphorylase after addition of amino acids was antagonized by Itu. (3) In contrast with amino acids, Itu increased neither the cell volume nor the aspartate and glutamate concentrations. (4) Itu enhanced the levels of cyclic AMP. The stimulation of glycogen deposition in the presence of Itu persisted when the cyclic AMP concentration was further increased by adenosine or 2-chloroadenosine. (5) Itu decreased the concentration of ATP, but its effects on glycogen synthesis, synthase a and phosphorylase a concentrations persisted when the ATP catabolism was prevented by adenosine. (6) The effect of Itu on glycogen synthesis was not the result of inhibition of adenosine kinase, since 5′-amino-5′-deoxyadenosine, another inhibitor of this enzyme, had no effect on glycogen deposition.

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Characterization of ionotrophic purinergic receptors in hepatocytes

et al. 2007

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Ionotrophic purinergic (P2X) receptors function as receptor-gated cation channels, where agonist binding leads to opening of a nonselective cation pore permeable to both Na ؉ and Ca 2؉ . Based on evidence that extracellular adenosine 5-triphosphate (ATP) stimulates glucose release from liver, these studies evaluate whether P2X receptors are expressed by hepatocytes and contribute to ATP-dependent calcium signaling and glucose release. Studies were performed in isolated hepatocytes from rats and mice and hepatoma cells from humans and rats. Transcripts and protein for both P2X4 and P2X7 were detectable, and immunohistochemistry of intact liver revealed P2X4 in the basolateral and canalicular domains. H epatocytes exhibit regulated release of adenosine 5Ј-triphosphate (ATP) into the extracellular space. 1 Once outside the cell, these nucleotides function as potent autocrine/paracrine signaling molecules that modulate liver function through activation of purinergic receptors in the plasma membrane. Initially discovered in neurons, purinergic receptors are implicated in the control of a spectrum of essential physiologic mechanisms ranging from vascular tone to programmed cell death. In the liver, nanomolar concentrations of ATP, or its breakdown products, activate Cl Ϫ channels, decrease cell volume, and stimulate bile flow. 2,3 Moreover, exposure of perfused isolated livers to ATP stimulates a large release of glucose. 4 Collectively, these coordinated pathways of ATP release, receptor binding, and degradation constitute a versatile mechanism for paracrine regulation of liver function.These diverse effects of ATP are not readily explained by a single receptor type. Previous studies indicate that hepatocytes express several subtypes of G-protein coupled P2Y receptors, including P2Y1, P2Y2, P2Y4, and P2Y6. Selective stimulation of P2Y2 receptors activates plasma membrane chloride channels and stimulates ductular bile secretion. 5 P2Y receptors also appear to play a role in the activation of glycogen phosphorylase, the rate-controlling enzyme in hepatic glycogenolysis, 6 and regulate multiple signaling pathways with changes in cellular [Ca 2ϩ ], eicosanoid production, and cyclic adenosine monophosphate

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Modulation of maximal glycogenolysis in perfused rat liver by adenosine and ATP

Cited by 16 publications

References 41 publications

Modulation of basal hepatic glycogenolysis by nitric oxide

Modulation of basal hepatic glycogenolysis by nitric oxide

Stimulation of rat liver glycogen synthesis by the adenosine kinase inhibitor 5-iodotubercidin

Characterization of ionotrophic purinergic receptors in hepatocytes

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