Control of glutamate release by complexes of adenosine and cannabinoid receptors
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| 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/10451/55356 |
Resumo: | © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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Control of glutamate release by complexes of adenosine and cannabinoid receptorsAdenosine A2A receptorAdenylyl cyclaseCannabinoid CB1 receptorGPCR heteromersGlutamate transmissionStriatum© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependence of A2AR signaling for the Gi protein-mediated CB1R signaling was described as one of its main biochemical characteristics. However, recent studies have questioned the localization of functionally significant A2AR-CB1R heteromers in striatal glutamatergic terminals. Results: Using a peptide-interfering approach combined with biophysical and biochemical techniques in mammalian transfected cells and computational modeling, we could establish a tetrameric quaternary structure of the A2AR-CB1R heterotetramer. This quaternary structure was different to the also tetrameric structure of heteromers of A2AR with adenosine A1 receptors or dopamine D2 receptors, with different heteromeric or homomeric interfaces. The specific quaternary structure of the A2A-CB1R, which depended on intermolecular interactions involving the long C-terminus of the A2AR, determined a significant A2AR and Gs protein-mediated constitutive activation of adenylyl cyclase. Using heteromer-interfering peptides in experiments with striatal glutamatergic terminals, we could then demonstrate the presence of functionally significant A2AR-CB1R heteromers with the same biochemical characteristics of those studied in mammalian transfected cells. First, either an A2AR agonist or an A2AR antagonist allosterically counteracted Gi-mediated CB1R agonist-induced inhibition of depolarization-induced glutamate release. Second, co-application of both an A2AR agonist and an antagonist cancelled each other effects. Finally, a CB1R agonist inhibited glutamate release dependent on a constitutive activation of A2AR by a canonical Gs-Gi antagonistic interaction at the adenylyl cyclase level. Conclusions: We demonstrate that the well-established cannabinoid-induced inhibition of striatal glutamate release can mostly be explained by a CB1R-mediated counteraction of the A2AR-mediated constitutive activation of adenylyl cyclase in the A2AR-CB1R heteromer.Work supported with the intramural funds of the National Institute on Drug Abuse, “Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación/FEDER” (SAF2015-74627-JIN, SAF2016-77830-R, SAF2017-87349-R) and ISCIII/FEDER (PIE14/00034), the Catalan government (2017 SGR 1604), “Fundació la Marató de TV3” (20152031), FWO (SBO-140028), “Fundação para a Ciência e a Tecnologia” (PTDC/DTP-FTO/3346/2014 and PTDC/MED-NEU/31274/2017), FEDER (QREN) through “Programa Operacional Factores de Competitividade” (COMPETE 2020, POCI-01-0145-FEDER-007440, CENTRO-01-0145-FEDER-000012-N2323P30, and UID/NEU/04539/2019), and through “Programa Mais Centro” (CENTRO-01-0246-FEDER-000010 and CENTRO-07-ST24-FEDER-002006).Springer NatureRepositório da Universidade de LisboaKöfalvi, AttilaMoreno, EstefaníaCordomí, ArnauCai, Ning-ShengFernández-Dueñas, VictorFerreira, Samira G.Guixà-González, RamónSánchez-Soto, MartaYano, HideakiCasadó-Anguera, VerònicaCunha, Rodrigo A.Sebastião, Ana MCiruela, FranciscoPardo, LeonardoCasadó, VicentFerré, Sergi2022-12-06T14:34:57Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55356engBMC Biol. 2020 Jan 23;18(1):910.1186/s12915-020-0739-01741-7007info: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:RCAAP2023-11-08T17:02:14Zoai:repositorio.ul.pt:10451/55356Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:00.924296Repositório 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 |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| title |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| spellingShingle |
Control of glutamate release by complexes of adenosine and cannabinoid receptors Köfalvi, Attila Adenosine A2A receptor Adenylyl cyclase Cannabinoid CB1 receptor GPCR heteromers Glutamate transmission Striatum |
| title_short |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| title_full |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| title_fullStr |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| title_full_unstemmed |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| title_sort |
Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| author |
Köfalvi, Attila |
| author_facet |
Köfalvi, Attila Moreno, Estefanía Cordomí, Arnau Cai, Ning-Sheng Fernández-Dueñas, Victor Ferreira, Samira G. Guixà-González, Ramón Sánchez-Soto, Marta Yano, Hideaki Casadó-Anguera, Verònica Cunha, Rodrigo A. Sebastião, Ana M Ciruela, Francisco Pardo, Leonardo Casadó, Vicent Ferré, Sergi |
| author_role |
author |
| author2 |
Moreno, Estefanía Cordomí, Arnau Cai, Ning-Sheng Fernández-Dueñas, Victor Ferreira, Samira G. Guixà-González, Ramón Sánchez-Soto, Marta Yano, Hideaki Casadó-Anguera, Verònica Cunha, Rodrigo A. Sebastião, Ana M Ciruela, Francisco Pardo, Leonardo Casadó, Vicent Ferré, Sergi |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Köfalvi, Attila Moreno, Estefanía Cordomí, Arnau Cai, Ning-Sheng Fernández-Dueñas, Victor Ferreira, Samira G. Guixà-González, Ramón Sánchez-Soto, Marta Yano, Hideaki Casadó-Anguera, Verònica Cunha, Rodrigo A. Sebastião, Ana M Ciruela, Francisco Pardo, Leonardo Casadó, Vicent Ferré, Sergi |
| dc.subject.por.fl_str_mv |
Adenosine A2A receptor Adenylyl cyclase Cannabinoid CB1 receptor GPCR heteromers Glutamate transmission Striatum |
| topic |
Adenosine A2A receptor Adenylyl cyclase Cannabinoid CB1 receptor GPCR heteromers Glutamate transmission Striatum |
| description |
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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2020 |
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2020 2020-01-01T00:00:00Z 2022-12-06T14:34:57Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/55356 |
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eng |
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eng |
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BMC Biol. 2020 Jan 23;18(1):9 10.1186/s12915-020-0739-0 1741-7007 |
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Springer Nature |
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Springer Nature |
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