{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T04:41:38Z","timestamp":1769316098475,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM123330"],"award-info":[{"award-number":["GM123330"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES005022"],"award-info":[{"award-number":["ES005022"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES007148"],"award-info":[{"award-number":["ES007148"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA072720"],"award-info":[{"award-number":["CA072720"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA046934"],"award-info":[{"award-number":["CA046934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA008748"],"award-info":[{"award-number":["CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK093903"],"award-info":[{"award-number":["DK093903"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03bcM) &gt; ondansetron &gt; granisetron &gt; tropisetron &gt; dolasetron (IC50: 85.4 \u03bcM) and the inhibition of ASP+ uptake by MATE1 in order of potency was ondansetron (IC50: 0.1 \u03bcM) &gt; palonosetron = tropisetron &gt; granisetron &gt; dolasetron (IC50: 27.4 \u03bcM). Ondansetron (0.5\u201320 \u03bcM) inhibited the basolateral-to-apical transcellular transport of ASP+ up to 64%. Higher concentrations (10 and 20 \u03bcM) 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 \u03bcM 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.<\/jats:p>","DOI":"10.3390\/ijms22126439","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T10:27:07Z","timestamp":1623839227000},"page":"6439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs"],"prefix":"10.3390","volume":"22","author":[{"given":"Blessy","family":"George","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar A.","family":"Jaimes","sequence":"additional","affiliation":[{"name":"Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie S.","family":"Joy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA"},{"name":"Cancer Center, University of Colorado, Aurora, CO 80045, USA"},{"name":"Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0032-1037","authenticated-orcid":false,"given":"Lauren M.","family":"Aleksunes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"ref_1","first-page":"32","article-title":"The biphasic effect of organic cations on the excretion of other organic cations","volume":"199","author":"Acara","year":"1976","journal-title":"J. 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