Membrane Permeability in the Gastrointestinal Tract: The Interplay between Microclimate pH and Transporters
Membrane Permeability in the Gastrointestinal Tract: The Interplay between Microclimate pH and Transporters
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DOI：
10.1002/cbdv.200900076
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发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Kristl, Albin
中科院分区：
文献类型：
--
作者：
Kristl, Albin
总结了在并排扩散池中测定的 pH 值和转运蛋白依赖性渗透性的一些例子。我们研究了单羧酸类药物通过切除的大鼠空肠组织和人工膜在粘膜到浆膜方向上的极化转运。我们确定，在体外，这些物质很可能不是通过单羧酸转运蛋白 1 转运的，而是通过被动 pH 依赖性转运转运的。我们还通过分离的大鼠肠段、Caco-2 细胞单层和人工膜研究了荧光素（一种低渗透性标记物）渗透性的各种影响。通过向粘膜侧添加D-葡萄糖，触发多药耐药性相关蛋白沿浆膜至粘膜方向穿过大鼠空肠的荧光素的极化转运，而荧光素流入的pH依赖性增加可能是单羧酸盐转运蛋白和有机阴离子转运多肽家族的成员的结果。通过大鼠小肠切除段的渗透性实验，我们确定环丙沙星是一种低渗透性药物，并且在粘膜至浆膜方向上比在相反方向上具有更高的且依赖于 pH 值的转运。我们还确定，氟喹诺酮类药物的渗透性及其在不同缓冲液中的溶解度均不受与金属阳离子相互作用的影响。
Some examples of pH- and transporter-dependent permeability, determined in side-by-side diffusion cells, are summarized. We investigated the polarized transport in the mucosal-to-serosal direction of monocarboxylic acid-type drugs through the excised rat jejunal tissue and an artificial membrane. We established that, in vitro, these substances are most probably not transported by monocarboxylate transporter 1, but by passive pH-dependent transport. We also studied various influences on the permeability of fluorescein, a low permeability marker, through isolated rat intestinal segments, Caco-2 cell monolayers, and an artificial membrane. Polarized transport of fluorescein in the serosal-to-mucosal direction through the rat jejunum by multidrug resistance-associated protein was triggered by the addition Of D-glucose to the mucosal side, while the pH-dependent increase of fluorescein influx is presumably the consequence of a monocarboxylate transporter and a member of the organic-anion transporting polypeptide family. With permeability experiments through the excised segments of rat small intestine, we ascertained that ciprofloxacin is a low-permeability drug and has higher and pH-dependent transport in the mucosal-to-serosal direction than in the opposite direction. We also established that neither the permeability of fluoroquinolones nor their solubility in different buffers was influenced by the interactions with metal cations.