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Adenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal neurons

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dc.contributor.authorMouro, Francisco
dc.contributor.authorRombo, Diogo M.
dc.contributor.authorDias, Raquel Baptista
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2021-07-22T15:26:43Z
dc.date.available2021-07-22T15:26:43Z
dc.date.issued2018
dc.description© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.pt_PT
dc.description.abstractBackground and purpose: NMDA receptors play a key role in both synaptic plasticity and neurodegeneration. Adenosine is an endogenous neuromodulator and through membrane receptors of the A2A subtype can influence both synaptic plasticity and neuronal death. The present work was designed to evaluate the influence of adenosine A2A receptors upon NMDA receptor activity in CA1 hippocampal neurons. We discriminated between modulation of synaptic versus extrasynaptic receptors, since extrasynaptic NMDA receptors are mostly associated with neurodegeneration while synaptic NMDA receptors are linked to plasticity phenomena. Experimental approach: Whole-cell patch-clamp recordings were obtained to evaluate NMDA receptor actions on CA1 pyramidal neurons of young adult (5-10 weeks) male Wistar rat hippocampus. Key results: Activation of A2A receptors with CGS 21680 (30 nM) consistently facilitated chemically-evoked NMDA receptor-currents (NMDA-PSCs) and afferent-evoked NMDA-currents (NMDA-EPSCs), an action prevented by an A2A receptor antagonist (SCH58261, 100 nM) and a PKA inhibitor, H-89 (1 μM). These actions did not reflect facilitation in glutamate release since there was no change in NMDA-EPSCs paired pulse ratio. A2A receptor actions were lost in the presence of an open-channel NMDA receptor blocker, MK-801 (10 μM), but persisted in the presence of memantine, at a concentration (10 μM) known to preferentially block extrasynaptic NMDA receptors. Conclusion and implications: These results show that A2A receptors exert a positive postsynaptic modulatory effect over synaptic, but not extrasynaptic, NMDA receptors in CA1 neurons and, therefore, under non-pathological conditions may contribute to shift the dual role of NMDA receptors towards enhancement of synaptic plasticity.pt_PT
dc.description.sponsorshipWork supported by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 (Programa Operacional Regional de Lisboa) from PORTUGAL 2020 and Fundação para a Ciência e Tecnologia, (FCT), by an FCT project (PTDC/DTP-FTO/3346/2014), and by a Twinning action (SynaNet) from the EU H2020 programme (project number: 692340). F.M.M. was in receipt of SFRH/BD/89582/2012 FTC fellowship, and D.M.R. is in receipt of a fellowship from Instituto de Medicina Molecular (IMM/BI/38-2017).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBr J Pharmacol. 2018 Dec;175(23):4386-4397pt_PT
dc.identifier.doi10.1111/bph.14497pt_PT
dc.identifier.eissn1476-5381
dc.identifier.issn0007-1188
dc.identifier.urihttp://hdl.handle.net/10451/49062
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationLISBOA-01-0145-FEDER-007391pt_PT
dc.relationSynaptic mechanisms involved in the brain cannabinoid actions and their modulation by adenosine receptors: implications for memory and mood control
dc.relationINTERACTION BETWEEN ADENOSINE A2A RECEPTORS AND CANNABINOID CB1 RECEPTORS AT THE HIPPOCAMPUS: CONSEQUENCES FOR PLASTICITY AND MEMORY
dc.relation.publisherversionhttps://bpspubs.onlinelibrary.wiley.com/journal/14765381pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.titleAdenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal neuronspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSynaptic mechanisms involved in the brain cannabinoid actions and their modulation by adenosine receptors: implications for memory and mood control
oaire.awardTitleINTERACTION BETWEEN ADENOSINE A2A RECEPTORS AND CANNABINOID CB1 RECEPTORS AT THE HIPPOCAMPUS: CONSEQUENCES FOR PLASTICITY AND MEMORY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F3346%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F89582%2F2012/PT
oaire.citation.endPage4397pt_PT
oaire.citation.issue23pt_PT
oaire.citation.startPage4386pt_PT
oaire.citation.titleBritish Journal of Pharmacologypt_PT
oaire.citation.volume175pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameMouro
person.familyNameRombo
person.familyNameDias
person.familyNameRibeiro
person.familyNameSebastião
person.givenNameFrancisco
person.givenNameDiogo
person.givenNameRaquel
person.givenNameJoaquim
person.givenNameAna M
person.identifier548147
person.identifier.ciencia-id081F-2518-907F
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0002-7141-8418
person.identifier.orcid0000-0002-9922-7381
person.identifier.orcid0000-0001-7921-405X
person.identifier.orcid0000-0002-9330-3507
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id54914036800
person.identifier.scopus-author-id35498669400
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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