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Transepithelial Transport of 4‐Chloro‐2‐Methylphenoxyacetic Acid (MCPA) across Human Intestinal C aco‐2 Cell Monolayers
Author(s) -
Kimura Osamu,
Tsukagoshi Kensuke,
Hayasaka Moriaki,
Endo Tetsuya
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2011.00850.x
Subject(s) - mcpa , chemistry , probenecid , paracellular transport , epithelial polarity , transcellular , apical membrane , membrane transport , caco 2 , biochemistry , biophysics , cell , membrane , biology , pharmacology , permeability (electromagnetism) , pesticide , agronomy
Mechanisms of transcellular transport of 4‐chloro‐2‐methylphenoxyacetic acid ( MCPA ) across the small intestine were investigated using C aco‐2 cells cultured on permeable membranes. The cell monolayers were incubated with MCPA , either from apical side at p H 6.0 or 7.4, or basolateral side at p H 7.4. The accumulation and apical‐to‐basolateral transport of MCPA were markedly stimulated by the acidic p H 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 C aco‐2 cell monolayers.