Takano M, Kato M, Takayama A, Yasuhara M, Inui K, Hori R
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
Biochim Biophys Acta. 1992 Jul 27;1108(2):133-9. doi: 10.1016/0005-2736(92)90017-g.
Transport of procainamide, an anti-arrhythmic drug, was investigated in LLC-PK1 kidney epithelial cell line. The uptake of procainamide by LLC-PK1 monolayers cultured in plastic dishes was temperature-dependent, saturable and inhibited by organic cations such as cimetidine and N-acetylprocainamide. An aminocephalosporin antibiotic, cephalexin, also inhibited procainamide uptake, but an organic anion, p-aminohippurate, did not. The uptake of procainamide was greater at an alkaline external pH than at an acidic pH. In addition, procainamide uptake increased when intracellular pH was decreased and the uptake decreased when the intracellular pH was increased by ammonium chloride treatment, indicating the involvement of an H+/procainamide antiport system in apical membrane. The basolateral to apical flux of procainamide across LLC-PK1 monolayers cultured on permeable supports was 2.5-times larger than the apical to basolateral flux, and only the former process was inhibited by other organic cations. These findings suggest that LLC-PK1 cells can transport procainamide by the organic cation transport system and that procainamide is transported unidirectionally from basolateral to apical side across the cell monolayers.
在LLC-PK1肾上皮细胞系中研究了抗心律失常药物普鲁卡因胺的转运。在塑料培养皿中培养的LLC-PK1单层细胞对普鲁卡因胺的摄取是温度依赖性的、可饱和的，并受到西咪替丁和N-乙酰普鲁卡因胺等有机阳离子的抑制。一种氨基头孢菌素抗生素头孢氨苄也抑制普鲁卡因胺的摄取，但有机阴离子对氨基马尿酸则没有此作用。在碱性细胞外pH条件下，普鲁卡因胺的摄取量大于酸性pH条件下的摄取量。此外，当细胞内pH降低时，普鲁卡因胺的摄取增加；而通过氯化铵处理使细胞内pH升高时，摄取减少，这表明顶端膜中存在H⁺/普鲁卡因胺反向转运系统。在可渗透支持物上培养的LLC-PK1单层细胞中，普鲁卡因胺从基底外侧到顶端的通量比从顶端到基底外侧的通量大约2.5倍，并且只有前一过程受到其他有机阳离子的抑制。这些发现表明，LLC-PK1细胞可以通过有机阳离子转运系统转运普鲁卡因胺，并且普鲁卡因胺在细胞单层中从基底外侧到顶端单向转运。
