Reference - Detail
| RRC ID | 43205 |
|---|---|
| Author | Kimura O, Tsukagoshi K, Endo T. |
| Title | Uptake of 4-chloro-2-methylphenoxyacetic acid (MCPA) from the apical membrane of Caco-2 cells by the monocarboxylic acid transporter. |
| Journal | Toxicol Appl Pharmacol |
| Abstract |
The cellular uptake mechanism of 4-chloro-2-methylphenoxyacetic acid (MCPA), a phenoxyacetic acid derivative, was investigated using Caco-2 epithelial cells. The cells were incubated with 50 microM MCPA at pH 6.0 and 37 degrees C, and the uptake of MCPA from the apical membranes was measured. The uptake of MCPA was significantly decreased by incubation at low temperature (4 degrees C) and markedly increased by lowering the extracellular pH. Pretreatment with a protonophore, carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone (25 microM), or metabolic inhibitors, 2,4-dinitrophenol (1 mM) and sodium azide (10 mM), significantly decreased the uptake of MCPA by 53%, 45% and 48%, respectively. Coincubation of MCPA with 10 mM l-lactic acid or alpha-cyano-4-hydroxycinnamate, which is a substrate or an inhibitor of the monocarboxylic acid transporters (MCTs), significantly decreased the uptake of MCPA by 31% and 20%, respectively, and coincubation with benzoic acid profoundly decreased the uptake by 68%. In contrast, coincubation with succinic acid (a dicarboxylic acid) did not affect the uptake. Kinetic analysis of initial MCPA uptake suggested that MCPA is taken up via a carrier-mediated process [Km=1.37+/-0.15 mM, Vmax=115+/-6 nmol (mg protein)(-1) (3 min)(-1)]. Lineweaver-Burk plots show that benzoic acid competitively inhibits the uptake of MCPA with a Ki value of 4.68 +/-1.76 mM. A trans-stimulation effect on MCPA uptake was found in cells preloaded with benzoic acid. These results suggest that the uptake of MCPA from the apical membrane of Caco-2 cells is mainly mediated by common MCTs along with benzoic acid but also in part by l-lactic acid. |
| Volume | 227(3) |
| Pages | 325-30 |
| Published | 2008-3-15 |
| DOI | 10.1016/j.taap.2007.10.028 |
| PII | S0041-008X(07)00502-9 |
| PMID | 18096194 |
| MeSH | 2,4-Dinitrophenol / pharmacology 2-Methyl-4-chlorophenoxyacetic Acid / antagonists & inhibitors 2-Methyl-4-chlorophenoxyacetic Acid / metabolism* Benzoic Acid / metabolism Benzoic Acid / pharmacology Biological Transport / drug effects Caco-2 Cells Carbonyl Cyanide m-Chlorophenyl Hydrazone / analogs & derivatives Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology Cell Membrane / drug effects Cell Membrane / metabolism* Cold Temperature Coumaric Acids / pharmacology Herbicides / metabolism* Humans Hydrogen-Ion Concentration Lactic Acid / metabolism Lactic Acid / pharmacology Monocarboxylic Acid Transporters / metabolism* Sodium Azide / pharmacology |
| IF | 3.347 |
| Times Cited | 10 |
| WOS Category | PHARMACOLOGY & PHARMACY TOXICOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Policy sources |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | CACO-2(RCB0988) |