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Cross-functioning between the extraneuronal monoamine transporter and multidrug resistance protein 1 in the uptake of adrenaline and export of 5-(glutathion-S-yl) adrenaline in rat cardiomyocytes

2008Journal article Restricted access
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dc.contributor.authorCosta, Vera Marisa
dc.contributor.authorFerreira, Luísa Maria
dc.contributor.authorBranco, Paula Sério
dc.contributor.authorCarvalho, Félix
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorCarvalho, Rui Albuquerque
dc.contributor.authorCarvalho, Márcia
dc.contributor.authorRemião, Fernando
dc.date.accessioned2021-07-01T16:51:48Z
dc.date.available2021-07-01T16:51:48Z
dc.date.issued2008
dc.description.abstractIsolated heart cells are highly susceptible to the toxicity of catecholamine oxidation products, namely, to catecholamine-glutathione adducts. Although cellular uptake and/or efflux of these products may constitute a crucial step, the knowledge about the involvement of transporters is still very scarce. This work aimed to contribute to the characterization of membrane transport mechanisms, namely, extraneuronal monoamine transporter (EMT), the multidrug resistant protein 1 (MRP1), and P-glycoprotein (P-gp) in freshly isolated cardiomyocytes from adult rats. These transporters may be accountable for uptake and/or efflux of adrenaline and an adrenaline oxidation product, 5-(glutathion-S-yl)adrenaline, in cardiomyocyte suspensions. Our results showed that 5-(glutathion-S-yl)adrenaline efflux was mediated by MRP1. Additionally, we demonstrated that the adduct formation occurs within the cardiomyocytes, since EMT inhibition reduced the intracellular adduct levels. The classical uptake2 transport in rat myocardial cells was inhibited by the typical EMT inhibitor, corticosterone, and surprisingly was also inhibited by low concentrations of another drug, a well-known P-gp inhibitor, GF120918. The P-gp activity was absent in the cells since P-gp-mediated efflux of quinidine was not blocked by GF120918. In conclusion, this work showed that freshly isolated cardiomyocytes from adult rats constitute a good model for the study of catecholamines and catecholamines metabolites membrane transport. The cardiomyocytes maintain EMT and MRP1 fully active, and these transporters contribute to the formation and efflux of 5-(glutathion-S-yl)adrenaline. In the present experimental conditions, P-gp activity is absent in the isolated cardiomyocytes.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1021/tx8002577pt_PT
dc.identifier.eissn1520-5010
dc.identifier.issn0893-228X
dc.identifier.urihttp://hdl.handle.net/10284/10008
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Chemical Societypt_PT
dc.relationThis work received financial support from the Portuguese State through “Fundação para a Ciência e Tecnologia” (FCT) (project PPCDT/SAU-OBS/55849/2004). V.M.C. acknowledges FCT for her Ph.D. grant (SFRD/BD/ 17677/ 2004) and GlaxoSmithKline for providing the GF120918.pt_PT
dc.subjectATP Binding Cassette Transporter, Subfamily B, Member 1pt_PT
dc.subjectAcridinespt_PT
dc.subjectAnimalspt_PT
dc.subjectCatecholaminespt_PT
dc.subjectCorticosteronept_PT
dc.subjectDeoxyepinephrinept_PT
dc.subjectEpinephrinept_PT
dc.subjectGlutathionept_PT
dc.subjectMalept_PT
dc.subjectMyocytes, Cardiacpt_PT
dc.subjectOrganic Cation Transport Proteinspt_PT
dc.subjectRatspt_PT
dc.subjectRats, Sprague-Dawleypt_PT
dc.subjectTetrahydroisoquinolinespt_PT
dc.titleCross-functioning between the extraneuronal monoamine transporter and multidrug resistance protein 1 in the uptake of adrenaline and export of 5-(glutathion-S-yl) adrenaline in rat cardiomyocytespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage135pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage129pt_PT
oaire.citation.titleChemical Research in Toxicologypt_PT
oaire.citation.volume22pt_PT
person.familyNameCarvalho
person.givenNameMarcia
person.identifier2017111
person.identifier.ciencia-id8B10-171E-E63E
person.identifier.orcid0000-0001-9884-4751
person.identifier.ridD-5999-2013
person.identifier.scopus-author-id7201413997
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3837b828-ba57-47f7-a811-cce65e4922c6
relation.isAuthorOfPublication.latestForDiscovery3837b828-ba57-47f7-a811-cce65e4922c6

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