Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes.

Bontemps, Françoise; Berghe, Georges; Hers, Henri‐Géry

doi:10.1073/pnas.80.10.2829

Cited by 106 publications

(70 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 60 min, the ATP as well as the glycogen content was higher in the presence of Itu and 2-chloroadenosine than with 2-chloroadenosine alone ( Figure 3). (iiii) 5'-amino-5'-deoxyadenosine, another inhibitor of adenosine kinase [1,2], had no effect on the formation of glycogen, although the ATP concentration was decreased by the agent (Table 2). From these results it can be concluded that the effect of Itu on glycogen synthesis cannot be explained by a decrease of the ATP concentration.…”

Section: Role Of Atp and Cyclic Ampmentioning

confidence: 97%

“…5-lodotubercidin (Itu) is a potent and selective inhibitor of adenosine kinase [1][2][3]. This enzyme is responsible for the phosphorylation of adenosine to AMP within the cells.…”

Section: Introductionmentioning

confidence: 99%

“…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]. Itu provokes ATP catabolism without modification of AMP or IMP concentrations [1].…”

Section: Introductionmentioning

confidence: 99%

“…Statistical differences (n = 3 or more cell preparations) were tested by Student's unpaired t test [29]. RESULTS Concentration-dependent effects of Itu in the presence and absence of amino acids The effects of Itu, an inhibitor of adenosine kinase [1][2][3], were studied in cells incubated for 60 min with substrates ( Figure 1). A mixture containing 10 mM glucose, 4.5 mM lactate and 0.5 mM pyruvate was chosen to study effects of Itu at various concentrations in the absence and presence of the amino acids glutamine, alanine and glycine (5 mM each).…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

Flückiger-Isler¹,

Walter²

1993

Biochemical Journal

View full text Add to dashboard Cite

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.

show abstract

Section: Role Of Atp and Cyclic Ampmentioning

confidence: 97%

“…5-lodotubercidin (Itu) is a potent and selective inhibitor of adenosine kinase [1][2][3]. This enzyme is responsible for the phosphorylation of adenosine to AMP within the cells.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Flückiger-Isler¹,

Walter²

1993

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Given the existence of an equilibrative transport system for adenosine, ADK fulfills the role of a metabolic reuptake system for adenosine, being the motor driving the influx of adenosine into the cell. The existence of a highly active substrate cycle between adenosine and AMP involving ADK and 5'-nucleotidase in brain allows minor changes in the activity of ADK to be translated rapidly into major changes in ambient adenosine (Arch and Newsholme, 1978;Bontemps et al, 1983). Thus, hypoxia-induced inhibition of ADK potentiated cardiac adenosine release (Decking et al, 1997), and pharmacological inhibition of ADK increased endogenous adenosine and depressed neuronal activity in hippocampal slices (Pak et al, 1994).…”

Section: Control Of Extracellular Adenosine By Intracellular Metabolimentioning

confidence: 99%

The adenosine kinase hypothesis of epileptogenesis

Boison

2008

Progress in Neurobiology

208

210

View full text Add to dashboard Cite

Current therapies for epilepsy are largely symptomatic and do not affect the underlying mechanisms of disease progression, i.e. epileptogenesis. Given the large percentage of pharmacoresistant chronic epilepsies, novel approaches are needed to understand and modify the underlying pathogenetic mechanisms. Although different types of brain injury (e.g. status epilepticus, traumatic brain injury, stroke) can trigger epileptogenesis, astrogliosis appears to be a homotypic response and hallmark of epilepsy. Indeed, recent findings indicate that epilepsy might be a disease of astrocyte dysfunction. This review focuses on the inhibitory neuromodulator and endogenous anticonvulsant adenosine, which is largely regulated by astrocytes and its key metabolic enzyme adenosine kinase (ADK). Recent findings support the "ADK hypothesis of epileptogenesis": (i) Mouse models of epileptogenesis suggest a sequence of events leading from initial downregulation of ADK and elevation of ambient adenosine as an acute protective response, to changes in astrocytic adenosine receptor expression, to astrocyte proliferation and hypertrophy (i.e. astrogliosis), to consequential overexpression of ADK, reduced adenosine and -finally -to spontaneous focal seizure activity restricted to regions of astrogliotic overexpression of ADK. (ii) Transgenic mice overexpressing ADK display increased sensitivity to brain injury and seizures. (iii) Inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. (iv) Intrahippocampal implants of stem cells engineered to lack ADK prevent epileptogenesis. Thus, ADK emerges both as a diagnostic marker to predict, as well as a prime therapeutic target to prevent, epileptogenesis.

show abstract

Sites and mechanism of adenosine formation in the cardiovascular system

Schrader

Decking

1998

Drug Dev. Res.

View full text Add to dashboard Cite

This review summarizes recent developments on the mechanisms by which adenosine is formed in the cardiovascular system. The concept is developed that AMP is both a precursor of adenosine but also a product when rephosphorylated by adenosine kinase. The functional significance of this metabolic cycle is the amplification of changes in free cytosolic adenosine, which translates a minor decrease of cardiac energetics in a substantial rise in adenosine. Furthermore, the metabolism of adenosine is highly compartmentalized, and the vascular endothelium forms an important metabolic barrier, which significantly influences the dose‐response curve for adenosine when this nucleoside is applied intervascularly. Inadequate supply of oxygen (critical PO2: 3 mm Hg) is the most important physiologic trigger for the formation of adenosine. In the range above the critical PO2, cardiomyocytes have the remarkable ability to down‐regulate their oxygen consumption before metabolic signs of hypoxia occur. Therefore, a reduction in oxygen supply as such is not a sufficient cause for the formation of adenosine but the imbalance between ATP formation and consumption. Future studies must resolve which factors govern the in‐vivo activity of adenosine kinase and 5′‐nucleotidase and how this is linked to the known physiologic effects of adenosine. Furthermore, the molecular mechanisms by which ATP can permeate through cell membranes and gives rise to the extracellular formation of adenosine need to be resolved. Drug Dev. Res. 45:288–294, 1998. © 1998 Wiley‐Liss, Inc.

show abstract

Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes.

Cited by 106 publications

References 33 publications

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

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

The adenosine kinase hypothesis of epileptogenesis

Sites and mechanism of adenosine formation in the cardiovascular system

Contact Info

Product

Resources

About