title: Transepithelial transport of 4-chloro-2-methylphenoxyacetic acid (MCPA) across human intestinal Caco-2 cell monolayers.
abstract: Mechanisms of transcellular transport of 4-chloro-2-methylphenoxyacetic acid (MCPA) across the small intestine were investigated using Caco-2 cells cultured on permeable membranes. The cell monolayers were incubated with MCPA, either from apical side at pH 6.0 or 7.4, or basolateral side at pH 7.4. The accumulation and apical-to-basolateral transport of MCPA were markedly stimulated by the acidic pH on the apical side (inwardly directed H(+) gradient), dependent on metabolic energy and inhibited by co-incubation with acetic acid or benzoic acid. Without the H(+) gradient, on the other hand, the basolateral-to-apical transport of MCPA (secretory transport) was higher than the apical-to-basolateral transport (absorptive transport), although the secretory transport of MCPA was markedly lower than the absorptive transport under the H(+) gradient. Co-incubation of MCPA with probenecid from the basolateral side significantly inhibited the accumulation and transport of MCPA, whereas co-incubation with p-aminohippuric acid did not. These results suggest that the absorptive transport of MCPA is mediated by H(+)-linked monocarboxylic acid transporters expressed on the apical membranes, while secretory transport is mediated by a probenecid-sensitive transporter expressed on the basolateral membranes of Caco-2 cell monolayers.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tsukagoshi
authors.forename: Moriaki
authors.initials: M
authors.lastname: Hayasaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Endo
mesh_terms: D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000378:metabolism*; D001692:Biological Transport; D018938:Caco-2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D011339:Probenecid / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D010130:p-Aminohippuric Acid / Q000494:pharmacology
chemical_list: D027501:Monocarboxylic Acid Transporters; D008456:2-Methyl-4-chlorophenoxyacetic Acid; D011339:Probenecid; D010130:p-Aminohippuric Acid