In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs

Int J Mol Sci. 2021 Jun 16;22(12):6439. doi: 10.3390/ijms22126439.


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.

Keywords: 5-HT3 antagonist; MATE1; OCT2; cationic; kidney; secretion; transport.

MeSH terms

  • Animals
  • Antiemetics / chemistry
  • Antiemetics / pharmacology*
  • Biological Transport / drug effects
  • Cell Line
  • Cells, Cultured
  • Dogs
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Madin Darby Canine Kidney Cells
  • Molecular Structure
  • Organic Cation Transport Proteins / biosynthesis*
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Organic Cation Transporter 2 / biosynthesis*
  • Organic Cation Transporter 2 / genetics
  • Serotonin 5-HT3 Receptor Antagonists / pharmacology


  • Antiemetics
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • SLC47A1 protein, human
  • Serotonin 5-HT3 Receptor Antagonists