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

• Published in: Molecular and cellular biochemistry 2017-04, Vol.428 (1-2), p.101-108
• Main Authors: Estrela, Gabriel R., Wasinski, Frederick, Felizardo, Raphael J. F., Souza, Laura L., Câmara, Niels O. S., Bader, Michael, Araujo, Ronaldo C.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - genetics; Acute Kidney Injury - prevention & control; Animals; Biochemistry; Biomedical and Life Sciences; Bradykinin B1 Receptor Antagonists - pharmacology; Cardiology; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; Cisplatin - pharmacokinetics; Disease Models, Animal; Gene Expression Regulation - drug effects; Gene Knockout Techniques; Kidney - drug effects; Kidney - metabolism; Kidneys; Life Sciences; Liver diseases; Male; Medical Biochemistry; Mice; Oncology; Organic Cation Transport Proteins - genetics; Organic Cation Transport Proteins - metabolism; Protein expression; Receptor, Bradykinin B1 - genetics; Receptor, Bradykinin B1 - metabolism; Renal function; Side effects
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-016-2920-x

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.