Sennoside-induced secretion is not caused by changes in mucosal permeability or Na+,K(+)-ATPase activity.
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.
Leng-Peschlow
E
E
Department of Pharmacology, Madaus AG, Köln, Germany.
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002400:Cathartics / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004896:Erythritol / Q000493:pharmacokinetics; D005260:Female; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012676:Senna Extract; D000081226:Sennosides; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000880:Anthraquinones; D002400:Cathartics; D000081226:Sennosides; D012676:Senna Extract; D012964:Sodium; D009247:NADH, NADPH Oxidoreductases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D004896:Erythritol; C020491:rhein