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Control of basal extracellular adenosine concentration in rat cerebellum
To re-examine how the basal extracellular concentration of adenosine is regulated in acutely isolated cerebellar slices we have combined electrophysiological and microelectrode biosensor measurements. In almost all cases, synaptic transmission was tonically inhibited by adenosine acting via A(1) rec...
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Formato: | Texto |
Lenguaje: | English |
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Blackwell Science Inc
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075308/ https://www.ncbi.nlm.nih.gov/pubmed/17446223 http://dx.doi.org/10.1113/jphysiol.2007.132050 |
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author | Wall, Mark J Atterbury, Alison Dale, Nicholas |
author_facet | Wall, Mark J Atterbury, Alison Dale, Nicholas |
author_sort | Wall, Mark J |
collection | PubMed |
description | To re-examine how the basal extracellular concentration of adenosine is regulated in acutely isolated cerebellar slices we have combined electrophysiological and microelectrode biosensor measurements. In almost all cases, synaptic transmission was tonically inhibited by adenosine acting via A(1) receptors. By contrast, in most slices, the biosensors did not measure an adenosine tone but did record a spatially non-uniform extracellular tone of the downstream metabolites (inosine and hypoxanthine). Most of the extracellular hypoxanthine arose from the metabolism of inosine by ecto-purine nucleoside phosphorylase (PNP). Adenosine kinase was the major determinant of adenosine levels, as its inhibition increased both adenosine concentration and A(1) receptor-mediated synaptic inhibition. Breakdown of adenosine by adenosine deaminase was the major source of the inosine/hypoxanthine tone. However adenosine deaminase played a minor role in determining the level of adenosine at synapses, suggesting a distal location. Blockade of adenosine transport (by NBTI/dipyridamole) had inconsistent effects on basal levels of adenosine and synaptic transmission. Unexpectedly, application of NBTI/dipyridamole prevented the efflux of adenosine resulting from block of adenosine kinase at only a subset of synapses. We conclude that there is spatial variation in the functional expression of NBTI/dipyridamole-sensitive transporters. The increased spatial and temporal resolution of the purine biosensor measurements has revealed the complexity of the control of adenosine and purine tone in the cerebellum. |
format | Text |
id | pubmed-2075308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Blackwell Science Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-20753082008-07-01 Control of basal extracellular adenosine concentration in rat cerebellum Wall, Mark J Atterbury, Alison Dale, Nicholas J Physiol Neuroscience To re-examine how the basal extracellular concentration of adenosine is regulated in acutely isolated cerebellar slices we have combined electrophysiological and microelectrode biosensor measurements. In almost all cases, synaptic transmission was tonically inhibited by adenosine acting via A(1) receptors. By contrast, in most slices, the biosensors did not measure an adenosine tone but did record a spatially non-uniform extracellular tone of the downstream metabolites (inosine and hypoxanthine). Most of the extracellular hypoxanthine arose from the metabolism of inosine by ecto-purine nucleoside phosphorylase (PNP). Adenosine kinase was the major determinant of adenosine levels, as its inhibition increased both adenosine concentration and A(1) receptor-mediated synaptic inhibition. Breakdown of adenosine by adenosine deaminase was the major source of the inosine/hypoxanthine tone. However adenosine deaminase played a minor role in determining the level of adenosine at synapses, suggesting a distal location. Blockade of adenosine transport (by NBTI/dipyridamole) had inconsistent effects on basal levels of adenosine and synaptic transmission. Unexpectedly, application of NBTI/dipyridamole prevented the efflux of adenosine resulting from block of adenosine kinase at only a subset of synapses. We conclude that there is spatial variation in the functional expression of NBTI/dipyridamole-sensitive transporters. The increased spatial and temporal resolution of the purine biosensor measurements has revealed the complexity of the control of adenosine and purine tone in the cerebellum. Blackwell Science Inc 2007-07-01 2007-04-19 /pmc/articles/PMC2075308/ /pubmed/17446223 http://dx.doi.org/10.1113/jphysiol.2007.132050 Text en © 2007 The Authors. Journal compilation © 2007 The Physiological Society |
spellingShingle | Neuroscience Wall, Mark J Atterbury, Alison Dale, Nicholas Control of basal extracellular adenosine concentration in rat cerebellum |
title | Control of basal extracellular adenosine concentration in rat cerebellum |
title_full | Control of basal extracellular adenosine concentration in rat cerebellum |
title_fullStr | Control of basal extracellular adenosine concentration in rat cerebellum |
title_full_unstemmed | Control of basal extracellular adenosine concentration in rat cerebellum |
title_short | Control of basal extracellular adenosine concentration in rat cerebellum |
title_sort | control of basal extracellular adenosine concentration in rat cerebellum |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075308/ https://www.ncbi.nlm.nih.gov/pubmed/17446223 http://dx.doi.org/10.1113/jphysiol.2007.132050 |
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