Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/27660 https://doi.org/10.1111/bph.12970 |
Resumo: | Background and Purpose Both CB1 cannabinoid and A2A adenosine receptors (CB1Rs and A2ARs) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A post-synaptic CB1R-A2AR interaction has already been unraveled, but the presynaptic A2AR-mediated control of presynaptic neuromodulation by CB1Rs remains to be defined. Since the corticostriatal terminals provide the major input of the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions. Experimental Approach Here we employ selective presynaptic tools to study the putative presynaptic interaction between the two neuromodulator systems. Pharmacological manipulation of CB1R and A2AR was carried out in isolated nerve terminals used for flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement, as well as in whole-cell patch-clamp recordings in horizontal corticostriatal slices. Results Flow synaptometry showed that A2AR are extensively co-localized with CB1R-immunopositive corticostriatal terminals, and A2AR co-immunoprecipitated CB1R in these purified terminals. A2AR activation decreased CB1R radioligand binding and decreased the CB1R-mediated inhibition of high-K+-evoked glutamate release in corticostriatal terminals. Accordingly, A2AR activation prevented CB1R-mediated paired-pulse facilitation and attenuated the CB1R-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices. Conclusions and Implications These results show that presynaptic A2AR dampens CB1R-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to shut-down the potent CB1R-mediated presynaptic inhibition, enabling a frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmissionBackground and Purpose Both CB1 cannabinoid and A2A adenosine receptors (CB1Rs and A2ARs) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A post-synaptic CB1R-A2AR interaction has already been unraveled, but the presynaptic A2AR-mediated control of presynaptic neuromodulation by CB1Rs remains to be defined. Since the corticostriatal terminals provide the major input of the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions. Experimental Approach Here we employ selective presynaptic tools to study the putative presynaptic interaction between the two neuromodulator systems. Pharmacological manipulation of CB1R and A2AR was carried out in isolated nerve terminals used for flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement, as well as in whole-cell patch-clamp recordings in horizontal corticostriatal slices. Results Flow synaptometry showed that A2AR are extensively co-localized with CB1R-immunopositive corticostriatal terminals, and A2AR co-immunoprecipitated CB1R in these purified terminals. A2AR activation decreased CB1R radioligand binding and decreased the CB1R-mediated inhibition of high-K+-evoked glutamate release in corticostriatal terminals. Accordingly, A2AR activation prevented CB1R-mediated paired-pulse facilitation and attenuated the CB1R-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices. Conclusions and Implications These results show that presynaptic A2AR dampens CB1R-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to shut-down the potent CB1R-mediated presynaptic inhibition, enabling a frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses.John Wiley & Sons, Inc.2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/27660http://hdl.handle.net/10316/27660https://doi.org/10.1111/bph.12970engFERREIRA, S. G. [et. al] - Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission. "British Journal of Pharmacology". ISSN 1476-5381. (2014)1476-5381http://onlinelibrary.wiley.com/doi/10.1111/bph.12970/abstractFerreira, S. G.Gonçalves, F. Q.Marques, J. M.Tomé, Â. R.Rodrigues, R. J.Nunes-Correia, I.Ledent, C.Harkany, T.Venance, L.Cunha, R. A.Köfalvi, A.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2021-11-04T10:43:27Zoai:estudogeral.uc.pt:10316/27660Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:53:36.674024Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
title |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
spellingShingle |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission Ferreira, S. G. |
title_short |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
title_full |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
title_fullStr |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
title_full_unstemmed |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
title_sort |
Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission |
author |
Ferreira, S. G. |
author_facet |
Ferreira, S. G. Gonçalves, F. Q. Marques, J. M. Tomé, Â. R. Rodrigues, R. J. Nunes-Correia, I. Ledent, C. Harkany, T. Venance, L. Cunha, R. A. Köfalvi, A. |
author_role |
author |
author2 |
Gonçalves, F. Q. Marques, J. M. Tomé, Â. R. Rodrigues, R. J. Nunes-Correia, I. Ledent, C. Harkany, T. Venance, L. Cunha, R. A. Köfalvi, A. |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Ferreira, S. G. Gonçalves, F. Q. Marques, J. M. Tomé, Â. R. Rodrigues, R. J. Nunes-Correia, I. Ledent, C. Harkany, T. Venance, L. Cunha, R. A. Köfalvi, A. |
description |
Background and Purpose Both CB1 cannabinoid and A2A adenosine receptors (CB1Rs and A2ARs) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A post-synaptic CB1R-A2AR interaction has already been unraveled, but the presynaptic A2AR-mediated control of presynaptic neuromodulation by CB1Rs remains to be defined. Since the corticostriatal terminals provide the major input of the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions. Experimental Approach Here we employ selective presynaptic tools to study the putative presynaptic interaction between the two neuromodulator systems. Pharmacological manipulation of CB1R and A2AR was carried out in isolated nerve terminals used for flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement, as well as in whole-cell patch-clamp recordings in horizontal corticostriatal slices. Results Flow synaptometry showed that A2AR are extensively co-localized with CB1R-immunopositive corticostriatal terminals, and A2AR co-immunoprecipitated CB1R in these purified terminals. A2AR activation decreased CB1R radioligand binding and decreased the CB1R-mediated inhibition of high-K+-evoked glutamate release in corticostriatal terminals. Accordingly, A2AR activation prevented CB1R-mediated paired-pulse facilitation and attenuated the CB1R-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices. Conclusions and Implications These results show that presynaptic A2AR dampens CB1R-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to shut-down the potent CB1R-mediated presynaptic inhibition, enabling a frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 |
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/10316/27660 http://hdl.handle.net/10316/27660 https://doi.org/10.1111/bph.12970 |
url |
http://hdl.handle.net/10316/27660 https://doi.org/10.1111/bph.12970 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
FERREIRA, S. G. [et. al] - Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission. "British Journal of Pharmacology". ISSN 1476-5381. (2014) 1476-5381 http://onlinelibrary.wiley.com/doi/10.1111/bph.12970/abstract |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
John Wiley & Sons, Inc. |
publisher.none.fl_str_mv |
John Wiley & Sons, Inc. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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