Molecular and Cellular Biochemistry

, Volume 428, Issue 1–2, pp 101–108 | Cite as

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

  • Gabriel R. Estrela
  • Frederick Wasinski
  • Raphael J. F. Felizardo
  • Laura L. Souza
  • Niels O. S. Câmara
  • Michael Bader
  • Ronaldo C. Araujo


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.


Cisplatin nephrotoxicity Organic transporters Kinins 



This work was supported by FAPESP grants 2013/06207-6, 2015/20082-7 and by CAPES/PROBRAL grant 7191/15-4.

Compliance with ethical standards

Conflict of interest

All the authors declared no competing interests.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Gabriel R. Estrela
    • 1
    • 2
  • Frederick Wasinski
    • 1
    • 2
  • Raphael J. F. Felizardo
    • 2
  • Laura L. Souza
    • 4
  • Niels O. S. Câmara
    • 3
  • Michael Bader
    • 4
  • Ronaldo C. Araujo
    • 1
    • 2
  1. 1.Department of BiophysicsFederal University of São PauloSão PauloBrazil
  2. 2.Department of Medicine, Division of NephrologyFederal University of São PauloSão PauloBrazil
  3. 3.Department of Immunology, Laboratory of Transplantation Immunobiology, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil
  4. 4.Max Delbrück Center for Molecular MedicineBerlinGermany

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