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
Autor(a) principal: | |
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Data de Publicação: | 2009 |
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/10316/10378 https://doi.org/10.1021/tx8002577 |
Resumo: | Isolated 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. |
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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 CardiomyocytesIsolated 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.American Chemical Society2009-01-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/10378http://hdl.handle.net/10316/10378https://doi.org/10.1021/tx8002577engChemical Research in Toxicology. 22:1 (2009) 129-1350893-228XCosta, Vera MarisaFerreira, Luísa MariaBranco, Paula SérioCarvalho, FélixBastos, Maria LourdesCarvalho, Rui AlbuquerqueCarvalho, MárciaRemião, Fernandoinfo: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:RCAAP2020-05-29T09:41:59Zoai:estudogeral.uc.pt:10316/10378Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:45.980921Repositório 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 |
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 |
title |
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 |
spellingShingle |
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 Costa, Vera Marisa |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
author |
Costa, Vera Marisa |
author_facet |
Costa, Vera Marisa Ferreira, Luísa Maria Branco, Paula Sério Carvalho, Félix Bastos, Maria Lourdes Carvalho, Rui Albuquerque Carvalho, Márcia Remião, Fernando |
author_role |
author |
author2 |
Ferreira, Luísa Maria Branco, Paula Sério Carvalho, Félix Bastos, Maria Lourdes Carvalho, Rui Albuquerque Carvalho, Márcia Remião, Fernando |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Costa, Vera Marisa Ferreira, Luísa Maria Branco, Paula Sério Carvalho, Félix Bastos, Maria Lourdes Carvalho, Rui Albuquerque Carvalho, Márcia Remião, Fernando |
description |
Isolated 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. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-01-19 |
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/10316/10378 http://hdl.handle.net/10316/10378 https://doi.org/10.1021/tx8002577 |
url |
http://hdl.handle.net/10316/10378 https://doi.org/10.1021/tx8002577 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Chemical Research in Toxicology. 22:1 (2009) 129-135 0893-228X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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