Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus
Autor(a) principal: | |
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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/10400.21/12401 |
Resumo: | Caffeine, 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. |
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Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampusCaffeineNMDARHippocampusA(1)adenosine receptorA(2A)adenosine receptorCaffeine, 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.SpringerRCIPLSilva Martins, RoberttaD.M., RomboRibeiro, JoanaMeneses, CarlosPeralva Borges Martins, Vladimir PedroRibeiro, Joaquim A.Vaz, Sandra H.Cussa Kubrusly, Regina CeliaSebastião, Ana M2020-11-25T15:02:51Z2020-122020-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/12401engMARTINS, 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. 503-5181573-953810.1007/s11302-020-09724-zmetadata only accessinfo: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:RCAAP2023-08-03T10:05:14Zoai:repositorio.ipl.pt:10400.21/12401Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:20:29.821340Repositório 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 |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
title |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
spellingShingle |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus Silva Martins, Robertta Caffeine NMDAR Hippocampus A(1)adenosine receptor A(2A)adenosine receptor |
title_short |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
title_full |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
title_fullStr |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
title_full_unstemmed |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
title_sort |
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus |
author |
Silva Martins, Robertta |
author_facet |
Silva Martins, Robertta D.M., Rombo Ribeiro, Joana Meneses, Carlos Peralva Borges Martins, Vladimir Pedro Ribeiro, Joaquim A. Vaz, Sandra H. Cussa Kubrusly, Regina Celia Sebastião, Ana M |
author_role |
author |
author2 |
D.M., Rombo Ribeiro, Joana Meneses, Carlos Peralva Borges Martins, Vladimir Pedro Ribeiro, Joaquim A. Vaz, Sandra H. Cussa Kubrusly, Regina Celia Sebastião, Ana M |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
RCIPL |
dc.contributor.author.fl_str_mv |
Silva Martins, Robertta D.M., Rombo Ribeiro, Joana Meneses, Carlos Peralva Borges Martins, Vladimir Pedro Ribeiro, Joaquim A. Vaz, Sandra H. Cussa Kubrusly, Regina Celia Sebastião, Ana M |
dc.subject.por.fl_str_mv |
Caffeine NMDAR Hippocampus A(1)adenosine receptor A(2A)adenosine receptor |
topic |
Caffeine NMDAR Hippocampus A(1)adenosine receptor A(2A)adenosine receptor |
description |
Caffeine, 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-11-25T15:02:51Z 2020-12 2020-12-01T00:00:00Z |
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/10400.21/12401 |
url |
http://hdl.handle.net/10400.21/12401 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
MARTINS, 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. 503-518 1573-9538 10.1007/s11302-020-09724-z |
dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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