title: Effect of diclofenac on SLC16A3/MCT4 by the Caco-2 cell line.
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.
authors.affiliation: 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.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: 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.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Futagi
authors.affiliation: 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.
authors.forename: Masaya
authors.initials: M
authors.lastname: Ideno
authors.affiliation: 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.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: 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.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Narumi
authors.affiliation: 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.
authors.forename: Ayako
authors.initials: A
authors.lastname: Furugen
authors.affiliation: 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: ken-i@pharm.hokudai.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D004008:Diclofenac / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; D004008:Diclofenac; D019344:Lactic Acid
keywords: Diclofenac; Lactic acid; Membrane; Oocyte; Transporter