Tomita Y, Takano M, Yasuhara M, Hori R, Inui K
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
J Pharmacol Exp Ther. 1995 Jan;272(1):63-9.
Transport of cephalosporins was studied using isolated rabbit intestinal epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+ exchanger, reduced the steady-state uptake of cephradine, suggesting that the exchanger contributes to the maintenance of an inward H+ gradient as a driving force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distribution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the transport activity was higher in the upper parts of the intestinal segments and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells in concentrative and reversible and that the H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for the active uptake of these drugs. The activity of the H+/dipeptide cotransporter should be higher in upper segments and in villus cells of the small intestine.
利用分离的兔肠上皮细胞研究了头孢菌素的转运。细胞对头孢拉定的摄取是浓缩性的，添加甘氨酰肌氨酸可抑制其摄取。添加质子载体羰基氰化物4-三氟甲氧基苯腙（FCCP）后，细胞内积累的头孢拉定从细胞中流出。钠氢交换体抑制剂氨氯地平降低了头孢拉定的稳态摄取，表明该交换体有助于维持内向氢离子梯度作为驱动力。ATP耗竭的肠细胞对头孢拉定的摄取由内向氢离子梯度主动驱动，并受到FCCP和甘氨酰肌氨酸的抑制。还在分离的细胞中检测了头孢拉定转运活性沿小肠和绒毛-隐窝轴的分布，在肠段上部和绒毛细胞中转运活性较高。这些结果表明，肠上皮细胞对口服头孢菌素的摄取是浓缩性且可逆的，氢离子/二肽共转运体和钠氢交换体对这些药物的主动摄取起重要作用。小肠上段和绒毛细胞中氢离子/二肽共转运体的活性应较高。
