EPITHELIAL TRANSPORT OF DRUGS IN CELL-CULTURE .2. EFFECT OF EXTRACELLULAR CALCIUM-CONCENTRATION ON THE PARACELLULAR TRANSPORT OF DRUGS OF DIFFERENT LIPOPHILICITIES ACROSS MONOLAYERS OF INTESTINAL EPITHELIAL (CACO-2) CELLS
EPITHELIAL TRANSPORT OF DRUGS IN CELL-CULTURE .2. EFFECT OF EXTRACELLULAR CALCIUM-CONCENTRATION ON THE PARACELLULAR TRANSPORT OF DRUGS OF DIFFERENT LIPOPHILICITIES ACROSS MONOLAYERS OF INTESTINAL EPITHELIAL (CACO-2) CELLS
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DOI：
10.1002/jps.2600790710
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发表时间：
1990-07-01
影响因子：
3.8
通讯作者：
MAGNUSSON, C
中科院分区：
文献类型：
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作者：
ARTURSSON, P;MAGNUSSON, C
以人肠道细胞系Caco-2为模型，研究了一系列具有不同亲脂性的同源药物(β-阻滞剂)在肠上皮细胞中的被动扩散。Caco-2单分子膜的通透性通过钙开关实验进行调节。跨膜阻力可以可逆地从.apprx.280 ohms.cntdot.cm2(类似于结肠上皮的阻力)降低到.apprx.60 ohms.cntdot.cm2(类似于小肠上皮的阻力)。透射电子显微镜显示，电导率的增加是由连接复合体成分的可逆分离引起的，而不是由细胞分离引起的。一般来说，细胞旁渗透性的增加导致更亲水的药物的表观渗透系数增加了2-9倍(例如，从0.20+-。0.010次。10-6至1.43+-0.185次。阿替洛尔为10-6 cm/S)，而较亲脂药物的转运参数保持不变(例如，43.03.+-)。3.64次。10-6和46.10+-。3.25次。心得安10-6 cm/S)。这些发现表明，在Caco-2模型中研究细胞旁途径对药物转运的贡献是可能的。
A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of a homologous series of drugs (.beta.-blocking agents) of different lipophilicity across intestinal epithelium. The permeability of the Caco-2 monoplayers was modulated by the use of a calcium switch assay. The transmembrane resistance could be reversibly decreased from .apprx.280 ohms.cntdot.cm2 (a resistance similar to that of colon epithelium) to .apprx.60 ohms.cntdot.cm2 (a resistance similar to that of small intestine epithelium). Transmission electron microscopy showed that the increased electrical permeability was caused by a reversible separation of the components of the junctional complex and not by cell detachment. In general, the increased paracellular permeability resulted in a 2- to 9-fold increase in the apparent permeability coefficients for the more hydrophilic drugs (e.g., from 0.20 .+-. 0.010 .times. 10-6 to 1.43 .+-. 0.185 .times. 10-6 cm/s for atenolol), while the transport parameters for the more lipophilic drugs remained unchanged (e.g., 43.03 .+-. 3.64 .times. 10-6 and 46.10 .+-. 3.25 .times. 10-6 cm/s for propranolol). These findings indicate that it is possible to study the contribution of the paracellular pathway to the transport of drugs in the Caco-2 model.