Tamai I, Takanaga H, Maeda H, Sai Y, Ogihara T, Higashida H, Tsuji A
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, School of Medicine, Kanazawa University, Japan.
Biochem Biophys Res Commun. 1995 Sep 14;214(2):482-9. doi: 10.1006/bbrc.1995.2312.
A molecular mechanism for the intestinal monocarboxylic acid transport was characterized by using a proton/monocarboxylate transporter, MCT1, in Chinese hamster ovary (CHO) cells, first found by Garcia et al. (Cell, 76, 865-873, 1994). Northern blotting analysis showed that MCT1-isomers exist in the rat and rabbit intestinal enterocytes and Caco-2 cells. The expression of [14C]lactic acid uptake by Xenopus laevis oocytes injected with rabbit intestinal mRNA was reduced by hybridizing the mRNA with a MCT1 cDNA of CHO cells before microinjection used as the antisense DNA. [14C]Lactic acid uptake by CHO cells was pH dependent, saturable, stereospecific, and reduced in the presence of acetic acid, benzoic acid, S- and R-ibuprofen, S- and R-mandelic acid, nicotinic acid, pravastatin, propionic acid and valproic acid. In addition, several monocarboxylic acids were transported in pH-dependent and saturable manners. These results suggest that the intestinal MCT1-related protein contributes to a carrier-mediated absorption for organic weak acid compounds.
利用质子/单羧酸转运体MCT1，对中国仓鼠卵巢（CHO）细胞中的肠道单羧酸转运分子机制进行了表征，该转运体最早由加西亚等人发现（《细胞》，第76卷，第865 - 873页，1994年）。Northern印迹分析表明，MCT1异构体存在于大鼠和兔的肠道肠上皮细胞以及Caco - 2细胞中。用CHO细胞的MCT1 cDNA作为反义DNA在显微注射前与兔肠道mRNA杂交，可降低注射了兔肠道mRNA的非洲爪蟾卵母细胞对[¹⁴C]乳酸的摄取表达。CHO细胞对[¹⁴C]乳酸的摄取具有pH依赖性、饱和性、立体特异性，并且在乙酸、苯甲酸、S - 和R - 布洛芬、S - 和R - 扁桃酸、烟酸、普伐他汀、丙酸和丙戊酸存在时会降低。此外，几种单羧酸以pH依赖性和饱和性方式进行转运。这些结果表明，肠道MCT1相关蛋白有助于有机弱酸化合物的载体介导吸收。
