Leng-Peschlow E
Department of Pharmacology, Madaus AG, Köln, Germany.
J Pharm Pharmacol. 1993 Nov;45(11):951-4. doi: 10.1111/j.2042-7158.1993.tb05633.x.
The effect of sennosides (50 mg kg-1) on the rat colon in-situ was studied 6 h after oral treatment when the laxative effect was maximal. In a second experiment, rhein (4 x 10(-3) M), an active sennoside metabolite, was administered into the lumen of the colon for 1 h. Both sennosides and rhein reduced net H2O and Na+ absorption or reversed it to net secretion. Paracellular permeability, as measured using erythritol as a small marker molecule, was increased 2- to 3-fold; permeability to a large molecule, PEG 1000, was unchanged. The activity of Na+,K(+)-ATPase in the colon mucosa was not affected. There was no damage of the epithelial cells as determined by lactic acid dehydrogenase release. These results indicate that neither inhibition of Na+,K(+)-ATPase nor damage of the colon epithelium are involved in the secretory effect of sennosides or rhein. The increased paracellular permeability of small molecules fits into the concept of stimulation of active chloride secretion by sennosides, which is electrochemically and osmotically balanced by an increase in Na+ and H2O flow via the paracellular pathway.
在口服给药6小时后，当泻下作用达到最大时，研究了番泻苷（50毫克/千克）对大鼠结肠原位的作用。在第二个实验中，将活性番泻苷代谢产物大黄酸（4×10⁻³ M）注入结肠腔1小时。番泻苷和大黄酸均降低了净水和钠的吸收，或将其逆转至净分泌。以赤藓糖醇作为小分子标记物测量的细胞旁通透性增加了2至3倍；对大分子聚乙二醇1000的通透性未改变。结肠黏膜中钠钾ATP酶的活性未受影响。通过乳酸脱氢酶释放测定，上皮细胞未受损。这些结果表明，番泻苷或大黄酸的分泌作用既不涉及钠钾ATP酶的抑制，也不涉及结肠上皮的损伤。小分子细胞旁通透性的增加符合番泻苷刺激活性氯分泌的概念，这通过细胞旁途径中钠和水流的增加在电化学和渗透方面达到平衡。
