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Caffeine has a dual influence on NMDA receptor–mediated glutamatergic transmission at the hippocampus

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dc.contributor.authorSilva Martins, Robertta
dc.contributor.authorRombo, Diogo M.
dc.contributor.authorGonçalves-Ribeiro, Joana
dc.contributor.authorMeneses, Carlos
dc.contributor.authorBorges-Martins, Vladimir P. P.
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorKubrusly, Regina C. C.
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2021-04-09T15:41:24Z
dc.date.available2021-04-09T15:41:24Z
dc.date.issued2020
dc.description© 2020 Springer Nature B.V.pt_PT
dc.description.abstractCaffeine, a stimulant largely consumed around the world, is a non-selective adenosine receptor antagonist, and therefore caffeine actions at synapses usually, but not always, mirror those of adenosine. Importantly, different adenosine receptors with opposing regulatory actions co-exist at synapses. Through both inhibitory and excitatory high-affinity receptors (A1R and A2R, respectively), adenosine affects NMDA receptor (NMDAR) function at the hippocampus, but surprisingly, there is a lack of knowledge on the effects of caffeine upon this ionotropic glutamatergic receptor deeply involved in both positive (plasticity) and negative (excitotoxicity) synaptic actions. We thus aimed to elucidate the effects of caffeine upon NMDAR-mediated excitatory post-synaptic currents (NMDAR-EPSCs), and its implications upon neuronal Ca2+ homeostasis. We found that caffeine (30-200 μM) facilitates NMDAR-EPSCs on pyramidal CA1 neurons from Balbc/ByJ male mice, an action mimicked, as well as occluded, by 1,3-dipropyl-cyclopentylxantine (DPCPX, 50 nM), thus likely mediated by blockade of inhibitory A1Rs. This action of caffeine cannot be attributed to a pre-synaptic facilitation of transmission because caffeine even increased paired-pulse facilitation of NMDA-EPSCs, indicative of an inhibition of neurotransmitter release. Adenosine A2ARs are involved in this likely pre-synaptic action since the effect of caffeine was mimicked by the A2AR antagonist, SCH58261 (50 nM). Furthermore, caffeine increased the frequency of Ca2+ transients in neuronal cell culture, an action mimicked by the A1R antagonist, DPCPX, and prevented by NMDAR blockade with AP5 (50 μM). Altogether, these results show for the first time an influence of caffeine on NMDA receptor activity at the hippocampus, with impact in neuronal Ca2+ homeostasis.pt_PT
dc.description.sponsorshipThe authors in Portugal are members of an EU twinning action (Project grant 952455). Robertta Silva Martins was in receipt of a fellowship from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro–FAPERJ, Brasil, Bolsa de Doutorado Sanduíche Europa/Oriente (grant number E-26/201.599/2018). The work was supported by Fundação para a Ciência e Tecnologia, Portugal (project grant PTDC/MED-FAR/30933/2017).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPurinergic Signal. 2020 Dec;16(4):503-518pt_PT
dc.identifier.doi10.1007/s11302-020-09724-zpt_PT
dc.identifier.eissn1573-9546
dc.identifier.issn1573-9538
dc.identifier.urihttp://hdl.handle.net/10451/47319
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationIn the search of the synaptic mechanism operated by a novel selective antiepileptic drug
dc.relationEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
dc.relation.publisherversionhttps://www.springer.com/journal/11302pt_PT
dc.subjectCaffeinept_PT
dc.subjectNMDARpt_PT
dc.subjectHippocampuspt_PT
dc.subjectA1 adenosine receptorpt_PT
dc.subjectA2A adenosine receptorpt_PT
dc.titleCaffeine has a dual influence on NMDA receptor–mediated glutamatergic transmission at the hippocampuspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIn the search of the synaptic mechanism operated by a novel selective antiepileptic drug
oaire.awardTitleEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-FAR%2F30933%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/952455/EU
oaire.citation.endPage518pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage503pt_PT
oaire.citation.titlePurinergic Signallingpt_PT
oaire.citation.volume16pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamH2020
person.familyNameSilva Martins
person.familyNameRombo
person.familyNameGonçalves Ribeiro
person.familyNameRibeiro
person.familyNameHenriques Vaz
person.familyNameSebastião
person.givenNameRobertta
person.givenNameDiogo
person.givenNameJoana Filipa
person.givenNameJoaquim
person.givenNameSandra Cristina
person.givenNameAna M
person.identifier.ciencia-id3018-692A-C792
person.identifier.ciencia-id081F-2518-907F
person.identifier.ciencia-id0E1C-952D-61BE
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0002-7177-7226
person.identifier.orcid0000-0002-9922-7381
person.identifier.orcid0000-0002-5194-6512
person.identifier.orcid0000-0002-9330-3507
person.identifier.orcid0000-0003-4258-9397
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id35498669400
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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