Ogihara T, Tamai I, Takanaga H, Sai Y, Tsuji A
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Pharm Res. 1996 Dec;13(12):1828-32. doi: 10.1023/a:1016081007981.
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.
The transport of monocarboxylic acids was examined using monolayers of human adenocarcinoma cell line, Caco-2 cells.
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.
Some chiral monocarboxylic acids are transported across the intestinal epithelial cells in a stereoselective manner by the specific carrier-mediated transport mechanism.
通过研究几种手性一元羧酸跨细胞转运的立体选择性，来表征一元羧酸跨肠上皮细胞的转运机制。
使用人腺癌细胞系Caco-2细胞单层来研究一元羧酸的转运。
示踪剂浓度（1微摩尔）下L-[14C]乳酸的渗透率呈现出pH和浓度依赖性，且显著高于D-异构体。L-/D-[14C]乳酸的渗透率均涉及可饱和和不可饱和过程；与D-异构体相比，可饱和过程对L-乳酸表现出更高的亲和力和更低的容量，而对于不可饱和过程，异构体之间未观察到差异。L-乳酸的转运受到手性一元羧酸如（R）/（S）-扁桃酸和（R）/（S）-布洛芬的立体选择性抑制。在L-乳酸和（S）-扁桃酸之间观察到相互竞争性抑制。
一些手性一元羧酸通过特定的载体介导转运机制以立体选择性方式跨肠上皮细胞转运。
