Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors

Bibliographic Details
Main Author: Cunha, Rodrigo A.
Publication Date: 1998
Other Authors: Sebastião, Ana M, Ribeiro, Joaquim A.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/7341
Summary: © 1998 Society for Neuroscience
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spelling Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptorsATPAdenosineEcto-nucleotidasesHippocampusA1 receptorsP2 receptors© 1998 Society for NeuroscienceATP analogs substituted in the γ-phosphorus (ATPγS, β, γ-imido-ATP, and β, γ-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices. ATP and γ-substituted analogs were equipotent to inhibit synaptic transmission in CA1 pyramid synapses (IC50 of 17–22 μM). The inhibitory effect of ATP and γ-phosphorus-substituted ATP analogs (30 μM) was not modified by the P2 receptor antagonist suramin (100 μM), was inhibited by 42–49% by the ecto-5’- nucleotidase inhibitor and α, β-methylene ADP (100 μM), was inhibited by 74–85% by 2 U/ml adenosine deaminase (which converts adenosine into its inactive metabolite-inosine), and was nearly prevented by the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 nM). Stronger support for the involvement of extracellular adenosine formation as a main requirement for the inhibitory effect of ATP and γ-substituted ATP analogs was the observation that an inhibitor of adenosine uptake, dipyridamole (20 μM), potentiated by 92–124% the inhibitory effect of ATP and γ-substituted ATP analogs (10 μM), a potentiation similar to that obtained for 10 μM adenosine (113%). Thus, the present results indicate that inhibition by extracellular ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ectonucleotidases and channeling of the generated adenosine to adenosine A1 receptors.This work was supported by Junta Nacional de Investigação Cientifica e Tecnológica, Praxis XXI, Gulbenkian Foundation, and European Union (BIOMED 2 programme)Society for NeuroscienceRepositório da Universidade de LisboaCunha, Rodrigo A.Sebastião, Ana MRibeiro, Joaquim A.2012-12-05T16:03:55Z19981998-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/7341engThe Journal of Neuroscience, March 15, 1998, 18(6):1987–19950270-6474http://www.jneurosci.org/content/18/6/1987.abstractinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T12:55:48Zoai:repositorio.ulisboa.pt:10451/7341Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T02:31:16.717557Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
title Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
spellingShingle Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
Cunha, Rodrigo A.
ATP
Adenosine
Ecto-nucleotidases
Hippocampus
A1 receptors
P2 receptors
title_short Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
title_full Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
title_fullStr Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
title_full_unstemmed Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
title_sort Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors
author Cunha, Rodrigo A.
author_facet Cunha, Rodrigo A.
Sebastião, Ana M
Ribeiro, Joaquim A.
author_role author
author2 Sebastião, Ana M
Ribeiro, Joaquim A.
author2_role author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Cunha, Rodrigo A.
Sebastião, Ana M
Ribeiro, Joaquim A.
dc.subject.por.fl_str_mv ATP
Adenosine
Ecto-nucleotidases
Hippocampus
A1 receptors
P2 receptors
topic ATP
Adenosine
Ecto-nucleotidases
Hippocampus
A1 receptors
P2 receptors
description © 1998 Society for Neuroscience
publishDate 1998
dc.date.none.fl_str_mv 1998
1998-01-01T00:00:00Z
2012-12-05T16:03:55Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/7341
url http://hdl.handle.net/10451/7341
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv The Journal of Neuroscience, March 15, 1998, 18(6):1987–1995
0270-6474
http://www.jneurosci.org/content/18/6/1987.abstract
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
_version_ 1833601392744333312

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