Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/10378
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
Authors: Costa, Vera Marisa 
Ferreira, Luísa Maria 
Branco, Paula Sério 
Carvalho, Félix 
Bastos, Maria Lourdes 
Carvalho, Rui Albuquerque 
Carvalho, Márcia 
Remião, Fernando 
Issue Date: 19-Jan-2009
Publisher: American Chemical Society
Citation: Chemical Research in Toxicology. 22:1 (2009) 129-135
Abstract: 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.
URI: https://hdl.handle.net/10316/10378
ISSN: 0893-228X
DOI: 10.1021/tx8002577
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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