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

2020-12Journal article Open access
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dc.contributor.authorSilva Martins, Robertta
dc.contributor.authorD.M., Rombo
dc.contributor.authorRibeiro, Joana
dc.contributor.authorMeneses, Carlos
dc.contributor.authorPeralva Borges Martins, Vladimir Pedro
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorCussa Kubrusly, Regina Celia
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2020-11-25T15:02:51Z
dc.date.available2020-11-25T15:02:51Z
dc.date.issued2020-12
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 (A(1)R and A(2)R, 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 Ca(2+)homeostasis. We found that caffeine (30-200 mu M) 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 A(1)Rs. 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 A(2A)Rs are involved in this likely pre-synaptic action since the effect of caffeine was mimicked by the A(2A)R antagonist, SCH58261 (50 nM). Furthermore, caffeine increased the frequency of Ca(2+)transients in neuronal cell culture, an action mimicked by the A(1)R antagonist, DPCPX, and prevented by NMDAR blockade with AP5 (50 mu M). Altogether, these results show for the first time an influence of caffeine on NMDA receptor activity at the hippocampus, with impact in neuronal Ca(2+)homeostasis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMARTINS, Robertta S.; [et al] – Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus. Purinergic Signalling. ISSN 1573-9538. Vol. 16, N.º 4 (2020), pp. 503-518pt_PT
dc.identifier.doi10.1007/s11302-020-09724-zpt_PT
dc.identifier.issn1573-9538
dc.identifier.issn1573-9546
dc.identifier.urihttp://hdl.handle.net/10400.21/12401
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.relationE-26/201.599/2018 - Fundação de Amparo a Pesquisa do Estado do Rio de Jan eiroFAPERJ, Brasil, Bolsa de Doutorado Sanduiche Europa/Orientept_PT
dc.relationPTDC/MED-FAR/30933/2017 - FCTpt_PT
dc.subjectCaffeinept_PT
dc.subjectNMDARpt_PT
dc.subjectHippocampuspt_PT
dc.subjectA(1)adenosine receptorpt_PT
dc.subjectA(2A)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.citation.endPage518pt_PT
oaire.citation.issue4
oaire.citation.startPage503pt_PT
oaire.citation.titlePurinergic Signallingpt_PT
oaire.citation.volume16
person.familyNameSilva Martins
person.familyNameRombo
person.familyNameRibeiro
person.familyNameMeneses
person.familyNamePeralva Borges Martins
person.familyNameVaz
person.familyNameCussa Kubrusly
person.familyNameSebastião
person.givenNameRobertta
person.givenNameDiogo
person.givenNameJoana
person.givenNameCarlos
person.givenNameVladimir Pedro
person.givenNameSandra
person.givenNameRegina Célia
person.givenNameAna M
person.identifier172273
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person.identifier.orcid0000-0002-7177-7226
person.identifier.orcid0000-0002-9922-7381
person.identifier.orcid0000-0002-5194-6512
person.identifier.orcid0000-0002-7770-7093
person.identifier.orcid0000-0002-5213-0363
person.identifier.orcid0000-0003-4258-9397
person.identifier.orcid0000-0002-6016-2197
person.identifier.orcid0000-0001-9030-6115
person.identifier.ridG-4515-2019
person.identifier.ridL-7393-2015
person.identifier.scopus-author-id14619857200
person.identifier.scopus-author-id6507327252
person.identifier.scopus-author-id7004409879
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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