Tamai I, Takanaga H, Maeda H, Yabuuchi H, Sai Y, Suzuki Y, Tsuji A
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
J Pharm Pharmacol. 1997 Jan;49(1):108-12. doi: 10.1111/j.2042-7158.1997.tb06762.x.
Intestinal brush-border membrane transport of monocarboxylic acids was investigated by using rabbit intestinal brush-border membrane vesicles (BBMVs) and isolated intestinal tissues mounted on Ussing-type chambers. [3H]Mevalonic acid uptake by BBMVs showed an overshoot phenomenon in the presence of an inwardly directed proton gradient, but not in the presence of an inwardly directed sodium gradient or an outwardly directed HCO3- or chloride gradient. Initial uptake of mevalonic acid was saturable in the presence of a proton gradient. Uptake of [3H]mevalonic acid was inhibited by various monocarboxylic acids, including acetic acid, benzoic acid, lactic acid, nicotinic acid, pravastatin, salicylic acid and valproic acid, but not by dicarboxylic acid or amino acids. Acetic acid, which is transported by both anion antiport and proton-coupled transport systems, induced serosal bicarbonate-dependent alkalinization in the mucosal-side bathing solution of rabbit jejunal tissues, when examined in Ussing-type chambers. Pravastatin, which is a structural analogue of mevalonic acid and is absorbed via proton-coupled transport like mevalonic acid, did not. The result demonstrates that acetic acid is transported by the bicarbonate-dependent anion antiport system, whereas pravastatin is not. So, it is suggested that monocarboxylic acids are transported by at least two independent transporters, namely, a proton-coupled transporter for most monocarboxylic acids, including mevalonic acid, pravastatin and acetic acid, and an anion antiporter for acetic acid, but not for mevalonic acid or pravastatin. Activation of anion antiporter can induce HCO3- secretion in intact intestine.
通过使用兔肠刷状缘膜囊泡（BBMVs）以及安装在Ussing型小室中的离体肠组织，研究了单羧酸的肠刷状缘膜转运。在存在内向质子梯度的情况下，BBMVs对[3H]甲羟戊酸的摄取显示出过冲现象，但在存在内向钠梯度或外向HCO3-或氯离子梯度时则没有。在存在质子梯度的情况下，甲羟戊酸的初始摄取是可饱和的。[3H]甲羟戊酸的摄取受到多种单羧酸的抑制，包括乙酸、苯甲酸、乳酸、烟酸、普伐他汀、水杨酸和丙戊酸，但不受二羧酸或氨基酸的抑制。当在Ussing型小室中进行检测时，通过阴离子反向转运和质子偶联转运系统都能转运的乙酸，在兔空肠组织的黏膜侧浴液中诱导了依赖于浆膜碳酸氢盐的碱化。而甲羟戊酸的结构类似物普伐他汀，像甲羟戊酸一样通过质子偶联转运被吸收，则没有这种现象。结果表明，乙酸是通过依赖于碳酸氢盐的阴离子反向转运系统转运的，而普伐他汀不是。因此，提示单羧酸至少由两种独立的转运体转运，即一种用于大多数单羧酸（包括甲羟戊酸、普伐他汀和乙酸）的质子偶联转运体，以及一种用于乙酸而不用于甲羟戊酸或普伐他汀的阴离子反向转运体。阴离子反向转运体的激活可诱导完整肠道中的HCO3-分泌。
