Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Biol Pharm Bull. 2010;33(8):1407-12. doi: 10.1248/bpb.33.1407.
The aim of the present study was to compare the membrane transport mechanisms of procainamide with those of quinidine using renal epithelial LLC-PK(1) and intestinal epithelial LS180 cells. In LLC-PK(1) cells, the transcellular transport of 10 microM quinidine in the basolateral-to-apical direction was similar to that in the opposite direction, and 1 mM tetraethylammonium (TEA) did not affect the transcellular transport of the drug. On the other hand, the transcellular transport of 10 microM TEA and procainamide in LLC-PK(1) cells was directional from the basolateral side to the apical side. In addition, this directional transcellular transport of procainamide was diminished in the presence of 1 mM TEA. In LS180 cells, the temperature-dependent cellular uptake of 100 microM quinidine and procainamide was markedly increased by alkalization of the apical medium, and was inhibited significantly by 1 mM several hydrophobic cationic drugs, but not by TEA. The rank order of the inhibitory effects of hydrophobic cationic drugs on the uptake of procainamide in LS180 cells was imipramine>quinidine>diphenhydramine asymptotically equal topyrilamine>procainamide, which was consistent with that on the uptake of quinidine. These findings suggested that procainamide (but not quinidine) was transported by cation transport systems in renal epithelial cells, but that both procainamide and quinidine were taken up by another cation transport system in intestinal epithelial cells.
本研究旨在比较普鲁卡因胺和奎尼丁的膜转运机制，采用肾上皮细胞 LLC-PK(1) 和肠上皮细胞 LS180 进行研究。在 LLC-PK(1) 细胞中，10μM 奎尼丁在基底外侧到顶端的跨细胞转运与相反方向相似，而 1mM 四乙铵 (TEA) 不影响药物的跨细胞转运。另一方面，10μM TEA 和普鲁卡因胺在 LLC-PK(1) 细胞中的跨细胞转运是从基底外侧到顶端的方向。此外，1mM TEA 的存在减弱了普鲁卡因胺的这种定向跨细胞转运。在 LS180 细胞中，100μM 奎尼丁和普鲁卡因胺的细胞摄取随顶端介质碱化而显著增加，并被 1mM 几种疏水性阳离子药物显著抑制，但 TEA 不抑制。疏水性阳离子药物对 LS180 细胞中普鲁卡因胺摄取的抑制作用的顺序为丙咪嗪>奎尼丁>苯海拉明渐次等于三甲嗪>普鲁卡因胺，这与奎尼丁的摄取一致。这些发现表明，普鲁卡因胺（而非奎尼丁）通过肾上皮细胞中的阳离子转运系统转运，但普鲁卡因胺和奎尼丁均被肠上皮细胞中的另一种阳离子转运系统摄取。
