In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs.
Int J Mol Sci
; 22(12)2021 Jun 16.
Article
em En
| MEDLINE
| ID: mdl-34208557
ABSTRACT
The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT3 antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT3 antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP+ was assessed using two models (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP+ uptake by OCT2 listed in order of potency was palonosetron (IC50 2.6 µM) > ondansetron > granisetron > tropisetron > dolasetron (IC50 85.4 µM) and the inhibition of ASP+ uptake by MATE1 in order of potency was ondansetron (IC50 0.1 µM) > palonosetron = tropisetron > granisetron > dolasetron (IC50 27.4 µM). Ondansetron (0.5-20 µM) inhibited the basolateral-to-apical transcellular transport of ASP+ up to 64%. Higher concentrations (10 and 20 µM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP+. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 µM caused significant intracellular accumulation of ASP+. Taken together, these data suggest that 5-HT3 antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte de Cátions Orgânicos
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Transportador 2 de Cátion Orgânico
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Rim
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Antieméticos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article