Nagai J, Takano M, Hirozane K, Yasuhara M, Inui K
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
J Pharmacol Exp Ther. 1995 Sep;274(3):1161-6.
Substrate specificity of the p-aminohippurate (PAH) transport system was investigated in the OK kidney epithelial cells. PAH uptake by OK cells from the basal side was inhibited by beta-lactam antibiotics such as benzylpenicillin (PCG) and cefazolin. The inhibition of PAH uptake by PCG was competitive and the Ki value was calculated as 108.8 microM. Transcellular transport of PCG across OK cell monolayers occurred unidirectionally from the basal to apical side, and transcellular transport and basolateral uptake were inhibited by PAH, probenecid and beta-lactam antibiotics. The basolateral uptake of cefazolin and cefotiam was also inhibited by PAH and probenecid. The basolateral uptake of PAH and PCG were not affected by aliphatic dicarboxylates with 3 or 4 carbon atoms, but were strongly inhibited by those with 5 or 6 carbon atoms. The inhibitory effect became weaker for a longer dicarboxylate with 7 carbon atoms, then increased again with increasing number of carbon atoms. Such a pattern of inhibition by dicarboxylates is essentially the same with that observed in rat renal proximal tubules in situ. These findings suggest that the PAH transport system in OK cells has a substrate specificity similar to that in rat renal proximal tubules, which is involved in the active secretion of various organic anions including drugs.
在OK肾上皮细胞中研究了对氨基马尿酸（PAH）转运系统的底物特异性。从基底侧摄取PAH的OK细胞受到β-内酰胺抗生素（如苄青霉素（PCG）和头孢唑啉）的抑制。PCG对PAH摄取的抑制作用具有竞争性，计算出的Ki值为108.8微摩尔。PCG跨OK细胞单层的跨细胞转运单向地从基底侧到顶端侧发生，并且跨细胞转运和基底外侧摄取受到PAH、丙磺舒和β-内酰胺抗生素的抑制。头孢唑啉和头孢替安的基底外侧摄取也受到PAH和丙磺舒的抑制。PAH和PCG的基底外侧摄取不受含3或4个碳原子的脂肪族二羧酸盐的影响，但受到含5或6个碳原子的脂肪族二羧酸盐的强烈抑制。对于含7个碳原子的更长的二羧酸盐，抑制作用变弱，然后随着碳原子数的增加再次增强。二羧酸盐的这种抑制模式与在大鼠原位肾近端小管中观察到的基本相同。这些发现表明，OK细胞中的PAH转运系统具有与大鼠肾近端小管中相似的底物特异性，该系统参与包括药物在内的各种有机阴离子的主动分泌。
