Journal ArticleDOI
Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism
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TLDR
The present results show that the microdialysis technique can be used to determine levels of purines in the extracellular fluid of defined brain regions in awake animals and that adenosine levels can be altered in vivo by inhibitors of adenoine transport and adenosines deaminase.Abstract:
The level of purines in the striatum of awake, freely moving rats was studied using microdialysis. The calculated extracellular concentration of adenosine and its metabolites inosine and hypoxanthine was very high immediately after implantation of the dialysis probe but decreased within 24 h to a level which remained stable for two days. Using in vitro calibration to determine the relative recovery of the dialysis probes we estimated resting levels in the striatal extracellular space to be 40, 110 and 580 nm, respectively. Inhibition of adenosine deaminase by deoxycoformycin produced a significant 1.4-fold increase in extracellular adenosine levels and a fall in inosine and hypoxanthine. A combination of three uptake blockers (dipyridamole, lidoflazine and nitrobenzylthioinosine), caused a 4.5-fold increase in extracellular adenosine levels without any change in inosine or hypoxanthine levels. After uptake inhibition deoxycoformycin did not have any significant effect. The present results show that the microdialysis technique can be used to determine levels of purines in the extracellular fluid of defined brain regions in awake animals. The high levels recorded during the first several hours after implantation may be artefactually high and reflect trauma. The results also show that adenosine levels can be altered in vivo by inhibitors of adenosine transport and adenosine deaminase. The present results indicate that the physiological adenosine level in striatal extracellular space is in the range 40–460 nm.read more
Citations
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The Role and Regulation of Adenosine in the Central Nervous System
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International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update
TL;DR: In the 10 years since the previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors, no developments have led to major changes in the recommendations, but there have been so many other developments that an update is needed.
Journal ArticleDOI
Adenosine in the central nervous system: release mechanisms and extracellular concentrations.
Serena Latini,Felicita Pedata +1 more
TL;DR: Key characteristics of adenosine release in the brain in response to different stimuli will be summarized, and studies performed to evaluateadenosine concentrations under physiological and hypoxic/ischemic conditions will be described to evaluate the degree of adenoine receptor activation.
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Adenosine receptors as drug targets — what are the challenges?
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References
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Journal ArticleDOI
The role of adenosine and its nucleotides in central synaptic transmission.
J.W. Phillis,P.H. Wu +1 more
Book ChapterDOI
The physiological role of adenosine in the central nervous system.
TL;DR: This chapter's attention is directed to the actions of adenosine and related purines in the CNS, and the receptors and biochemical actions that underlie these functional responses and behavioral responses to purinergic drugs are considered.
Journal ArticleDOI
Modulation of neurotransmission by purine nucleotides and nucleosides.
Bertil B. Fredholm,Per Hedqvist +1 more
Journal ArticleDOI
Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro.
TL;DR: A mathematical framework was developed to provide a quantitative basis for either in vivo tissue or in vitro microdialysis, and the importance of metabolism and efflux to the microvasculature is illustrated by the wide variation in predicted tissue concentration profiles.
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