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Carrier-mediated transport of monocarboxylic acids in BeWo cell monolayers as a model of the human trophoblast.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 1999 Dec; Vol. 88 (12), pp. 1288-92. - Publication Year :
- 1999
-
Abstract
- The monolayer-forming, human choriocarcinoma cell line, BeWo, was used to study the mechanisms of monocarboxylic acid transport across the human trophoblast. Benzoic acid, acetic acid, and lactic acid were used as markers for monocarboxylic acid carrier-mediated transport. The uptake of benzoic acid by BeWo cells was saturable (K(t) = 0.6 +/- 0.3 mM) at higher concentrations and significantly inhibited by typical metabolic inhibitors, sodium azide and 2, 4-dinitrophenol. A selection of different monocarboxylic acids, including a natural substrate lactic acid, also substantially inhibited the uptake of benzoic acid and acetic acid by BeWo cells, whereas dicarboxylic acids did not affect the uptake of either marker. Monocarboxylic acid uptake was pH-dependent and inhibited by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore. Kinetic analysis using Lineweaver-Burk plots revealed that monocarboxylic acids competitively inhibited the uptake of benzoic, lactic, and acetic acid by BeWo cells. In transport experiments, the permeation of benzoic acid from apical-to-basolateral side was greater than the permeation from the basolateral-to-apical side, and the transport of benzoic acid from apical-to-basolateral side was inhibited by monocarboxylic acids. The findings obtained in the present study confirm the existence of an asymmetric, carrier-mediated transport system for monocarboxylic acids across the BeWo cell, a representative of the human trophoblast.
- Subjects :
- Antimetabolites pharmacology
Benzoic Acid metabolism
Biological Transport, Active drug effects
Biological Transport, Active physiology
Biomarkers
Carboxylic Acids pharmacokinetics
Carboxylic Acids pharmacology
Cell Line
Humans
Kinetics
Models, Biological
Permeability
Trophoblasts cytology
Trophoblasts drug effects
Carboxylic Acids metabolism
Carrier Proteins metabolism
Trophoblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3549
- Volume :
- 88
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 10585224
- Full Text :
- https://doi.org/10.1021/js990173q