MATE-1 modulation by kinin B1 receptor enhances cisplatin efflux from renal cells

MATE-1 modulation by kinin B1 receptor enhances cisplatin efflux from renal cells

Author Estrela, Gabriel R. Autor UNIFESP Google Scholar
Wasinski, Frederick Autor UNIFESP Google Scholar
Felizardo, Raphael J. F. Autor UNIFESP Google Scholar
Souza, Laura L. Google Scholar
Camara, Niels O. S. Google Scholar
Bader, Michael Google Scholar
Araujo, Ronaldo C. Autor UNIFESP Google Scholar
Abstract Cisplatin is a drug widely used in chemotherapy that frequently causes severe renal dysfunction. Organic transporters have an important role to control the absorption and excretion of cisplatin in renal cells. Deletion and blockage of kinin B1 receptor has already been show to protect against cisplatin-induced acute kidney injury. To test whether it exerts its protective function by modulating the organic transporters in kidney, we studied kinin B1 receptor knockout mice and treatment with a receptor antagonist at basal state and in presence of cisplatin. Cisplatin administration caused downregulation of renal organic transporters

in B1 receptor knockout mice, this downregulation of organic transporters in kidney was absent

and treatment by a B1 receptor antagonist attenuated the downregulation of the transporter MATE-1. Moreover, kinin B1 receptor deletion and blockage at basal state resulted in higher renal expression of MATE-1. Moreover we observed that kinin B1 receptor deletion and blockage result in less accumulation of platinum in renal tissue. Thus, we propose that B1 receptor deletion and blockage protect the kidney from cisplatin-induced acute kidney injury by upregulating the expression of MATE-1, thereby increasing the efflux of cisplatin from renal cells.
Keywords Cisplatin nephrotoxicity
Organic transporters
xmlui.dri2xhtml.METS-1.0.item-coverage Dordrecht
Language English
Sponsor FAPESP
Grant number FAPESP: 2013/06207-6
FAPESP: 2015/20082-7
CAPES/PROBRAL: 7191/15-4
Date 2017
Published in Molecular And Cellular Biochemistry. Dordrecht, v. 428, p. 101-108, 2017.
ISSN 0300-8177 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 101-108
Access rights Closed access
Type Article
Web of Science ID WOS:000399249400009

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