Stereoselective and carrier-mediated transport of monocarboxylic acids across Caco-2 cells.
OBJECTIVE
To characterize the transport mechanism of monocarboxylic acids across intestinal epithelial cells by examining the stereoselectivity of the transcellular transport of several chiral monocarboxylic acids.


METHODS
The transport of monocarboxylic acids was examined using monolayers of human adenocarcinoma cell line, Caco-2 cells.


RESULTS
The permeability of L-[14C]lactic acid at a tracer concentration (1 microM) exhibited pH- and concentration-dependencies and was significantly greater than that of the D-isomer. The permeabilities of both L-/D-[14C]lactic acids involve saturable and nonsaturable processes; the saturable process showed a higher affinity and a lower capacity for L-lactic acid compared with the D-isomer, while no difference between the isomers was seen for the nonsaturable process. The transport of L-lactic acid was inhibited by chiral monocarboxylic acids such as (R)/ (S)-mandelic acids and (R)/(S)-ibuprofen in a stereoselective manner. Mutually competitive inhibition was observed between L-lactic acid and (S)-mandelic acid.


CONCLUSIONS
Some chiral monocarboxylic acids are transported across the intestinal epithelial cells in a stereoselective manner by the specific carrier-mediated transport mechanism.
Ogihara
T
T
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Tamai
I
I
Takanaga
H
H
Sai
Y
Y
Tsuji
A
A
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D008333:Mandelic Acids / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013237:Stereoisomerism
D007773:Lactates; D008333:Mandelic Acids; D012964:Sodium; C037938:mandelic acid; D007052:Ibuprofen