Adenosine Release

Stone, T.W.; Newby, Andrew C.; Lloyd, H.G.E.

doi:10.1007/978-1-4612-4504-9_6

Cited by 19 publications

(13 citation statements)

References 194 publications

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“…Because AK is thought to provide the major route for the removal of intracellular adenosine under normal circumstances, this result suggests that NMDA increases intracellular production of adenosine, in addition to its inhibition of adenosine removal. Sources of intracellular adenosine include cAMP (following its hydrolysis to 5′‐AMP by cyclic nucleotide phosphodiesterases), ATP and S‐adenosylhomocysteine (following its hydrolysis to adenosine and homocysteine by S‐adenosylhomocysteine hydrolase; Stone et al ., 1990; Moriwaki et al ., 1999). In addition, intracellular adenosine concentration could also be increased by inhibiting the removal of adenosine by a pathway other than AK, for example adenosine deaminase (White, 1996; Moriwaki et al ., 1999).…”

Section: Discussionmentioning

confidence: 99%

NMDA receptor‐mediated extracellular adenosine accumulation in rat forebrain neurons in culture is associated with inhibition of adenosine kinase

Chung

Wang

et al. 2003

Eur J of Neuroscience

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The effect of N-methyl-d-aspartate (NMDA) on regulation of extracellular adenosine was investigated in rat forebrain neurons in culture. NMDA evoked accumulation of extracellular adenosine with an EC50 value of 4.8 +/- 1.2 microM. The effect of NMDA was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5,10-imine hydrogen maleate indicating that NMDA receptor activation was involved. The NMDA effect was also blocked by chelation of extracellular Ca2+ indicating that influx of calcium was required. The nitric oxide-cyclic GMP signalling pathway was not involved, as nitric oxide synthase inhibitors were unable to block, and cGMP analogs were unable to mimic, the effect of NMDA. The source for extracellular adenosine was likely to be intracellular adenosine as the ecto-5'-nucleotidase inhibitor alpha beta-methylene-ADP was unable to block the effect of NMDA. One possible cause of intracellular adenosine accumulation might be NMDA receptor-mediated inhibition of mitochondrial function and ATP hydrolysis. We found that NMDA caused a concentration dependent depletion of intracellular ATP with an EC50 value of 21 +/- 8 microM. NMDA also caused a significant decrease in adenosine kinase activity, assayed by two different methods. Consistent with the hypothesis that inhibition of adenosine kinase is sufficient to cause an increase in extracellular adenosine, inhibition of adenosine kinase by 5'-iodotubercidin resulted in elevation of extracellular adenosine. However, in the presence of a concentration of 5'-iodotubercidin that inhibited over 90% of adenosine kinase activity, exposure to NMDA still caused adenosine accumulation. These studies suggest that several possible mechanisms are likely to be involved in NMDA-evoked extracellular adenosine accumulation.

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Section: Discussionmentioning

confidence: 99%

NMDA receptor‐mediated extracellular adenosine accumulation in rat forebrain neurons in culture is associated with inhibition of adenosine kinase

Chung

Wang

et al. 2003

Eur J of Neuroscience

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“…Another possible explanation is that the purines increased the concentration of extracellular adenosine. Adenosine is released from cells under a variety of circumstances (Stone et al, 1990). The concentration of adenosine in the extracellular fluid of brain is about 1.0 p M (Zetterstrom et al, 1982) and is removed from the extracellular fluid by metabolism and re-uptake into cells.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of astrocyte proliferation by purine and pyrimidine nucleotides and nucleosides

Christjanson

Middlemiss

Rathbone

1993

Glia

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Proliferation of brain astrocytes as a result of cell death has been well documented in vivo. Dying cells release purine and pyrimidine nucleosides and nucleotides and their deoxy derivatives both from soluble intracellular pools and from DNA and RNA. Previously, we have observed that purine nucleosides and nucleotides stimulate chick astrocyte proliferation in vitro. To further our analysis, we questioned whether pyrimidines or the deoxy derivatives of purine nucleosides and nucleotides might also be astrocyte mitogens. Pyrimidine nucleosides, nucleotides, and their deoxynucleotide derivatives were uniformly inactive. In contrast, deoxyguanosine, deoxyadenosine, and their mono-, di-, and triphosphates stimulated thymidine incorporation into astrocytes at concentrations similar to those at which their ribonucleoside and ribonucleotide analogues were active. Inosine, IMP, ITP, and hypoxanthine were active, whereas xanthine and xanthosine were not. However, XMP, XDP, and XTP stimulated thymidine incorporation. The effects of the nucleosides and deoxynucleosides were inhibited by antagonists of adenosine A2 receptors. These data indicate that most purine nucleosides, deoxynucleosides, and their 5' mono, di-, and triphosphate derivatives released from damaged cells are capable of stimulating astrocyte proliferation in vitro and may contribute to astrocyte proliferation in vivo following injury to the CNS.

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“…However, this is not the only route by which adenosine reaches the extracellular space; it is also produced by the metabolism of extracellular nucleotides, including ATP, 5'-adenosine monophosphate (5' AMP) and adenosine 3':5'-cyclic monophosphate (cyclic AMP), (Stone et al, 1990;Meghji, 1991) the efflux of which does not involve the nucleoside transporter. The net effect of a loss of transport activity would therefore be an elevation of extracellular adenosine concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly adipocytes from diabetic animals have a reduced sensitivity to adenosine (Solomon et al, 1987;Green & Johnson, 1991). Adenosine is now well recognised as an ubiquitous neuromodulator (Stone, 1991;Stone & Simmonds, 1991) which is released from many tissue during normal cellular activity (White & Hoehn, 1991) and which acts both presynaptically, to depress neurotransmitter release, and postsynaptically to modify cellular activity in a direction which tends to oppose or preclude the development of hypoxic stress (Stone et al, 1990). Any change in the function of adenosine receptors centrally could, therefore, have a variety of secondary effects on other transmitter systems and on behaviour.…”

Section: Introductionmentioning

confidence: 99%

Changes in adenosine sensitivity in the hippocampus of rats with streptozotocin‐induced diabetes

Morrison

MacKinnon

Bartrup

et al. 1992

British J Pharmacology

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1Hippocampal slices have been used to assess the sensitivity of the CNS to adenosine and yaminobutyric acid (GABA) in diabetes. The effects of adenosine, 2-chloroadenosine, GABA, muscimol and baclofen were studied on orthodromic synaptic potentials recorded in the CAl region of slices taken from normal rats or animals made diabetic by the injection of streptozotocin. 2 In diabetic animals the sensitivity to adenosine was increased 4 fold compared with normal rats. The potency of 2-chloroadenosine was unchanged. 3 The nucleoside transport inhibitor, hydroxynitrobenzylthioinosine (HNBTI), increased the potency of adenosine in slices from normal rats but not in slices from diabetic rats. 4 No change was observed in the potency of GABA or muscimol, although a small but significant decrease was detected in the ECM value for baclofen.5 Treatment of diabetic animals with insulin restored the potency of adenosine to control levels. 6 It is concluded that the diabetic state is accompanied by substantial changes of adenosine sensitivity due to the loss of nucleoside uptake processes. Secondary neurochemical changes followingfrom this in human diabetic patients may contribute to the reported behavioural changes.

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Adenosine Release

Cited by 19 publications

References 194 publications

NMDA receptor‐mediated extracellular adenosine accumulation in rat forebrain neurons in culture is associated with inhibition of adenosine kinase

NMDA receptor‐mediated extracellular adenosine accumulation in rat forebrain neurons in culture is associated with inhibition of adenosine kinase

Stimulation of astrocyte proliferation by purine and pyrimidine nucleotides and nucleosides

Changes in adenosine sensitivity in the hippocampus of rats with streptozotocin‐induced diabetes

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