T. Ogihara et al., In situ and in vitro evidence for stereoselective and carrier-mediated transport of monocarboxylic acids across intestinal epithelial tissue, BIOL PHAR B, 23(7), 2000, pp. 855-859
The present study was designed to establish the significance of carrier-med
iated transport in the intestinal absorption of monocarboxylic acids by exa
mining the stereoselectivity of transepithelial transport of chiral monocar
boxylic acids. The transport of L- and D-lactic acids was examined in vitro
using rat intestinal tissue sheets and in situ by means of intra-jejunal a
dministration, followed by measurement of the plasma concentration. Both th
e absorptive and secretory transport of L-[C-14]lactic acid across the inte
stinal epithelial tissues of rats was significantly greater than that of th
e D-isomer. The secretory transport of the L-isomer was significantly great
er than the absorptive transport, implying net transport in the secretory d
irection. When L- and D-[C-14]lactic acids were administered to the rat jej
unum, the absorption ratio of the L-isomer was lower than that of the D-iso
mer at 15 min after administration. The concentration-dependence of absorpt
ion for both L- and D-[C-14]lactic acids indicated the involvement of both
saturable and nonsaturable processes. The saturable process showed a higher
affinity and lower capacity for L-lactic acid compared with the D-isomer,
while no significant difference between the isomers was observed in the non
saturable process. The absorption of L-lactic acid was inhibited by chiral
2-hydroxymonocarboxylic acids in a stereoselective manner. Chiral monocarbo
xylic acids were shown to cross the intestinal epithelial tissues and to be
absorbed in a stereoselective manner after oral administration, suggesting
the involvement of specific carrier-mediated transport mechanism(s) in the
ir intestinal absorption in vivo.