Fagerholm U, Nilsson D, Knutson L, Lennernäs H
Department of Pharmacy, Uppsala University, Sweden.
Acta Physiol Scand. 1999 Mar;165(3):315-24. doi: 10.1046/j.1365-201x.1999.00510.x.
The mechanisms controlling rates and routes for intestinal absorption of nutrients and small compounds are still not fully clarified. In the present study we aimed to investigate the effect of solvent drag on intestinal permeability of compounds with different molecular sizes in humans and rats. The effective intestinal permeabilities (Peff) of hydrophilic compounds (MW 60-4000) were determined in the single-pass perfused jejunum in humans in vivo and rats in situ under iso- and hypotonic conditions. The transport mechanism(s) of water and the importance of the solvent drag effect were investigated by the use of D2O. This is the first report in humans establishing the relation between in vivo measured jejunal Peff and molecular size for hydrophilic compounds. In addition, in rats we also found a molecular-size selectivity for hydrophilic compounds similar to man. The jejunal Peff of water and urea (MW 60) in both species were several times higher than predicted from their physicochemical properties. In humans, the jejunal absorption of urea and creatinine (MW 113) was increased by solvent drag, while no effect was found for the other investigated compounds. In rats, Peff for urea and creatinine were unaffected. In conclusion, it is still unclear if solvent drag occurs mainly through the para- or transcellular route, although, results from this study further add to our earlier reports suggesting that the transcellular route is most important from a quantitative point of view regardless of physicochemical properties of the transported compounds.
控制营养物质和小分子化合物肠道吸收速率及途径的机制仍未完全阐明。在本研究中，我们旨在探究溶剂拖曳对人和大鼠中不同分子大小化合物肠道通透性的影响。在等渗和低渗条件下，于人体体内单通道灌注空肠和大鼠原位测定了亲水性化合物（分子量60 - 4000）的有效肠道通透性（Peff）。通过使用重水研究了水的转运机制及溶剂拖曳效应的重要性。这是首篇在人体中建立体内测定的空肠Peff与亲水性化合物分子大小之间关系的报告。此外，在大鼠中我们也发现了亲水性化合物与人类相似的分子大小选择性。两种物种中水和尿素（分子量60）的空肠Peff均比根据其物理化学性质预测的值高出数倍。在人体中，尿素和肌酐（分子量113）的空肠吸收因溶剂拖曳而增加，而其他研究的化合物未发现此效应。在大鼠中，尿素和肌酐的Peff未受影响。总之，溶剂拖曳主要是通过细胞旁途径还是跨细胞途径发生仍不清楚，尽管本研究结果进一步补充了我们之前的报告，表明从定量角度来看，无论转运化合物的物理化学性质如何，跨细胞途径都是最重要的。
