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Comparative effects of aluminum and ouabain on synaptosomal choline uptake, acetylcholine release and (Na+/K+)ATPase

dc.contributor.authorSilva, Virgília S.
dc.contributor.authorNunes, M. Alexandra
dc.contributor.authorCordeiro, J. Miguel
dc.contributor.authorCalejo, Ana I.
dc.contributor.authorSantos, Sofia
dc.contributor.authorNeves, Paulo
dc.contributor.authorSykes, António V.
dc.contributor.authorMorgado, Fernando
dc.contributor.authorDunant, Yves
dc.contributor.authorGonçalves, Paula P.
dc.date.accessioned2018-11-12T11:59:43Z
dc.date.available2018-11-12T11:59:43Z
dc.date.issued2007
dc.description.abstractClosing the gap between adverse health effects of aluminum and its mechanisms of action still represents a huge challenge. Cholinergic dysfunction has been implicated in neuronal injury induced by aluminum. Previously reported data also indicate that in vivo and in vitro exposure to aluminum inhibits the mammalian (Na(+)/K(+))ATPase, an ubiquitous plasma membrane pump. This study was undertaken with the specific aim of determining whether in vitro exposure to AlCl(3) and ouabain, the foremost utilized selective inhibitor of (Na(+)/K(+))ATPase, induce similar functional modifications of cholinergic presynaptic nerve terminals, by comparing their effects on choline uptake, acetylcholine release and (Na(+)/K(+))ATPase activity, on subcellular fractions enriched in synaptic nerve endings isolated from rat brain, cuttlefish optic lobe and torpedo electric organ. Results obtained show that choline uptake by rat synaptosomes was inhibited by submillimolar AlCl(3), whereas the amount of choline taken up by synaptosomes isolated from cuttlefish and torpedo remained unchanged. Conversely, choline uptake was reduced by ouabain to a large extent in all synaptosomal preparations analyzed. In contrast to ouabain, which modified the K(+) depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions, AlCl(3) induced reduction of stimulated acetylcholine release was only observed when rat synaptosomes were challenged. Finally, it was observed that the aluminum effect on cuttlefish and torpedo synaptosomal (Na(+)/K(+))ATPase activity was slight when compared to its inhibitory action on mammalian (Na(+)/K(+))ATPase. In conclusion, inhibition of (Na(+)/K(+))ATPase by AlCl(3) and ouabain jeopardized the high-affinity (Na(+)-dependent, hemicholinium-3 sensitive) uptake of choline and the Ca(2+)-dependent, K(+) depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions. The effects of submillimolar AlCl(3) on choline uptake and acetylcholine release only resembled those of ouabain when rat synaptosomes were assayed. Therefore, important differences were found between the species regarding the cholinotoxic action of aluminum. The variability of (Na(+)/K(+))ATPase sensitivity to aluminum of cholinergic neurons might contribute to their differential susceptibility to this neurotoxic agent.pt_PT
dc.description.sponsorshipQLK1-CT2002-00172
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.tox.2007.04.017pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/10931
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationThe synaptosome as a screening tool in Ecotoxicology
dc.relationNEUROTOXICIDADE DO ALUMÍNIO: O SINAPTOSSOMA COMO MODELO DE ESTUDO
dc.relationDISTRIBUIÇÃO, ESTRUTURA E FUNÇÃO DO ANTIPORTE DE CA2+/H+ DAS VESÍCULAS SINÁPTICAS NO CÉREBRO
dc.relationEFEITO DA TRANSLOCAÇÃO CATIÓNICA MEDIADA POR VESÍCULAS SINÁPTICAS NA NEUROTRANSMISSÃO
dc.relationMOLECULAR STUDY OF GENETIC CODE AMBIGUITY IN CANDIDA ALBICANS
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAcetylcholinept_PT
dc.subjectAluminum compoundspt_PT
dc.subjectAmino acid sequencept_PT
dc.subjectAnimalspt_PT
dc.subjectBrainpt_PT
dc.subjectCation transport proteinspt_PT
dc.subjectCell fractionationpt_PT
dc.subjectChloridespt_PT
dc.subjectCholinept_PT
dc.subjectDecapodiformespt_PT
dc.subjectDose-response relationshippt_PT
dc.subjectDrug combinationspt_PT
dc.subjectElectric organpt_PT
dc.subjectEnzyme inhibitorspt_PT
dc.subjectIn vitro techniquespt_PT
dc.subjectMalept_PT
dc.subjectMolecular sequence datapt_PT
dc.subjectOptic lobept_PT
dc.subjectOuabainpt_PT
dc.subjectRatspt_PT
dc.subjectRatspt_PT
dc.subjectSequence alignmentpt_PT
dc.subjectSodium-potassium-exchanging ATPasept_PT
dc.subjectSynaptosomespt_PT
dc.subjectTorpedopt_PT
dc.subjectWistarpt_PT
dc.subjectDrugpt_PT
dc.subjectNonmammalianpt_PT
dc.titleComparative effects of aluminum and ouabain on synaptosomal choline uptake, acetylcholine release and (Na+/K+)ATPasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleThe synaptosome as a screening tool in Ecotoxicology
oaire.awardTitleNEUROTOXICIDADE DO ALUMÍNIO: O SINAPTOSSOMA COMO MODELO DE ESTUDO
oaire.awardTitleDISTRIBUIÇÃO, ESTRUTURA E FUNÇÃO DO ANTIPORTE DE CA2+/H+ DAS VESÍCULAS SINÁPTICAS NO CÉREBRO
oaire.awardTitleEFEITO DA TRANSLOCAÇÃO CATIÓNICA MEDIADA POR VESÍCULAS SINÁPTICAS NA NEUROTRANSMISSÃO
oaire.awardTitleMOLECULAR STUDY OF GENETIC CODE AMBIGUITY IN CANDIDA ALBICANS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCTI%2FBSE%2F46721%2F2002/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBPD%2F14677%2F2003/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCTI/SFRH%2FBD%2F1079%2F2000/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F6403%2F2001/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F18101%2F2004/PT
oaire.citation.endPage177pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage158pt_PT
oaire.citation.titleToxicologypt_PT
oaire.citation.volume236pt_PT
oaire.fundingStreamPOCI
oaire.fundingStreamFARH
oaire.fundingStreamPOCTI
person.familyNameSykes
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person.identifier.ridC-3609-2012
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
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project.funder.nameFundação para a Ciência e a Tecnologia
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rcaap.rightsrestrictedAccesspt_PT
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