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Effect of diclofenac on SLC16A3/MCT4 by the Caco-2 cell line.

Authors
  • Sasaki, Shotaro1
  • Futagi, Yuya1
  • Ideno, Masaya1
  • Kobayashi, Masaki1
  • Narumi, Katsuya1
  • Furugen, Ayako1
  • Iseki, Ken2
  • 1 Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan. , (Japan)
  • 2 Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan; Department of Pharmacy, Hokkaido University Hospital, Sapporo 060-8648, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
Drug metabolism and pharmacokinetics
Publication Date
June 2016
Volume
31
Issue
3
Pages
218–223
Identifiers
DOI: 10.1016/j.dmpk.2016.03.004
PMID: 27236641
Source
Medline
Keywords
License
Unknown

Abstract

In the present study, we demonstrated that monocarboxylate transporter 4 (MCT4) is functionally expressed in Caco-2 cells. We studied the effects of 4 nonsteroidal anti-inflammatory drugs on the uptake of l-lactate as a good substrate of MCT4 by the cells. The monocarboxylate drugs inhibited the uptake of l-lactate into the cells. Diclofenac, as a member of the aryl-acetic acid group of nonsteroidal anti-inflammatory drugs, was the most potent inhibitor, with an inhibition constant of 20 μM. In the next study, we determined the type of inhibition for diclofenac. An l-lactate carrier is non-competitively inhibitable by the drug. We also demonstrated, in Xenopus oocyte expression system, potential of diclofenac for MCT4 inhibitor. The present results could provide a useful tool to discover MCT4-specific inhibitors.

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