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In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs.
- Source :
- International Journal of Molecular Sciences; Jun2021, Vol. 22 Issue 12, p6439, 1p
- Publication Year :
- 2021
-
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-HT<subscript>3</subscript> 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-HT<subscript>3</subscript> antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP<superscript>+</superscript> 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<superscript>+</superscript> uptake by OCT2 listed in order of potency was palonosetron (IC<subscript>50</subscript>: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC<subscript>50</subscript>: 85.4 μM) and the inhibition of ASP<superscript>+</superscript> uptake by MATE1 in order of potency was ondansetron (IC<subscript>50</subscript>: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC<subscript>50</subscript>: 27.4 μM). Ondansetron (0.5–20 μM) inhibited the basolateral-to-apical transcellular transport of ASP<superscript>+</superscript> up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP<superscript>+</superscript>. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP<superscript>+</superscript>. Taken together, these data suggest that 5-HT<subscript>3</subscript> antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 22
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 151140503
- Full Text :
- https://doi.org/10.3390/ijms22126439