title: Steric hindrance of 2,6-disubstituted benzoic acid derivatives on the uptake via monocarboxylic acid transporters from the apical membranes of Caco-2 cells.
abstract: Benzoic acid is a typical substrate for monocarboxylic acid transporters (MCTs), and easily taken up from the apical membranes of Caco-2 cells by MCTs. However, some benzoic acid derivatives were sparingly taken up by Caco-2 cells. To elucidate the mechanism of lower uptake of the derivatives, we investigated the effect of substitution of benzene ring on the uptake by MCTs using Caco-2 cells. Among the benzoic acid derivatives tested, the uptake of 2,6-disubstituted benzoic acids was markedly lower than that of other benzoic acids. Co-incubation of the 2,6-disubstituted derivatives with benzoic acid did not decrease the uptake of benzoic acid, while co-incubation with other derivatives significantly decreased the uptake of benzoic acid. Kinetic analyses elucidated that the uptake of 2,6-dichlorobenzoic acid and 2,3,6-trichlorobenzoic acid did not involve the carrier-mediated process. The 2,6-disubstitution of benzoic acid may prevent the access of carboxylic acid group to MCTs expressed on the apical membranes of Caco-2 cells.
authors.affiliation: Hijirigaoka Hospital, 214-22 Funaoka, Date, Hokkaido 052-0014, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tsukagoshi
authors.affiliation: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.affiliation: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. Electronic address: endotty@hoku-iryo-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Endo
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry* / Q000378:metabolism*; D001692:Biological Transport; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006540:Herbicides / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D015394:Molecular Structure; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D006540:Herbicides; D027501:Monocarboxylic Acid Transporters; D019817:Benzoic Acid
keywords: 2,6-Dichlorobenzoic acid; Benzoic acid; Caco-2 cells; Monocarboxylic acid transporters (MCTs); Steric hindrance