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VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways

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dc.contributor.authorCunha-Reis, Diana
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorAlmeida, Rodrigo F.M. De
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2022-12-06T15:45:32Z
dc.date.available2022-12-06T15:45:32Z
dc.date.issued2017
dc.description© 2017 The British Pharmacological Societypt_PT
dc.description.abstractBackground and purpose: Vasoactive intestinal peptide (VIP) is an important modulator of hippocampal synaptic transmission that influences both GABAergic synaptic transmission and glutamatergic cell excitability through activation of VPAC1 and VPAC2 receptors. Presynaptic enhancement of GABA release contributes to VIP modulation of hippocampal synaptic transmission. Experimental approach: We investigated which VIP receptors and coupled transduction pathways were involved in VIP enhancement of K+ -evoked [3 H]-GABA release from isolated nerve terminals of rat hippocampus. Key results: VIP enhancement of [3 H]-GABA release was potentiated in the presence of the VPAC1 receptor antagonist PG 97-269 but converted into an inhibition in the presence of the VPAC2 receptor antagonist PG 99-465, suggesting that activation of VPAC1 receptors inhibits and activation of VPAC2 receptors enhances, GABA release. A VPAC1 receptor agonist inhibited exocytotic voltage-gated calcium channel (VGCC)-dependent [3 H]-GABA release through activation of protein Gi/o , an effect also dependent on PKC activity. A VPAC2 receptor agonist enhanced both exocytotic VGCC-dependent release through protein Gs -dependent, PKA-dependent and PKC-dependent mechanisms and GABA transporter 1-mediated [3 H]-GABA release through a Gs protein-dependent and PKC-dependent mechanism. Conclusions and implications: Our results show that VPAC1 and VPAC2 VIP receptors have opposing actions on GABA release from hippocampal nerve terminals through activation of different transduction pathways. As VPAC1 and VPAC2 receptors are located in different layers of Ammon's horn, our results suggest that these VIP receptors underlie different modulation of synaptic transmission to pyramidal cell dendrites and cell bodies, with important consequences for their possible therapeutic application in the treatment of epilepsy.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e a Tecnologia: research grants: PTDC/SAU-NEU/103639/2008 and UID/MULTI/00612/2013; fellowships: SFRH/BPD/34661/2007 and SFRH/BPD/81358/2011.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBr J Pharmacol. 2017 Dec;174(24):4725-4737pt_PT
dc.identifier.doi10.1111/bph.14051pt_PT
dc.identifier.eissn1476-5381
dc.identifier.issn0007-1188
dc.identifier.urihttp://hdl.handle.net/10451/55362
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationCenter of Chemistry and Biochemistry
dc.relationROLE OF VIP CONTAINING INTERNEURONES IN THE CONTROL OF THE RAT HIPPOCAMPAL CIRCUITS DURING LOCOMOTION, EXPLORATION AND IN EPILEPSY
dc.relationEVALUATING THERAPEUTIC OPPORTUNITIES FOR PREVENTING EPILEPTOGENESIS, COGNITIVE DECLINE AND SUDDEN DEATH IN EPILEPSY
dc.relation.publisherversionhttps://bpspubs.onlinelibrary.wiley.com/journal/14765381pt_PT
dc.titleVPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathwayspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCenter of Chemistry and Biochemistry
oaire.awardTitleROLE OF VIP CONTAINING INTERNEURONES IN THE CONTROL OF THE RAT HIPPOCAMPAL CIRCUITS DURING LOCOMOTION, EXPLORATION AND IN EPILEPSY
oaire.awardTitleEVALUATING THERAPEUTIC OPPORTUNITIES FOR PREVENTING EPILEPTOGENESIS, COGNITIVE DECLINE AND SUDDEN DEATH IN EPILEPSY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-NEU%2F103639%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F00612%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/PIDDAC/SFRH%2FBPD%2F34661%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F81358%2F2011/PT
oaire.citation.endPage4737pt_PT
oaire.citation.issue24pt_PT
oaire.citation.startPage4725pt_PT
oaire.citation.titleBritish Journal of Pharmacologypt_PT
oaire.citation.volume174pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamPIDDAC
oaire.fundingStreamOE
person.familyNameJerónimo da Cunha Reis
person.familyNameRibeiro
person.familyNamede Almeida
person.familyNameSebastião
person.givenNameDiana Lina
person.givenNameJoaquim
person.givenNameRodrigo
person.givenNameAna M
person.identifierF-1689-2011
person.identifier.ciencia-id1F1E-73C0-FD44
person.identifier.ciencia-id081F-2518-907F
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0002-0900-9306
person.identifier.orcid0000-0002-9330-3507
person.identifier.orcid0000-0002-9748-7083
person.identifier.orcid0000-0001-9030-6115
person.identifier.ridD-8629-2012
person.identifier.scopus-author-id8571270200
person.identifier.scopus-author-id35498669400
person.identifier.scopus-author-id7005256125
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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