Intestinal filtration as a consequence of increased mucosal hydraulic permeability

Abstract

Two mechanisms have been proposed to explain the secretory action of laxative compounds in the intestine: 1. increase of the intracellular amount of cyclic adenosine monophosphate due to stimulation of the adenylate cyclase system and 2. inhibition of intestinal transfer processes, in particular the Na,K-ATPase activated sodium absorption. In a set of in vivo and in vitro experiments in rat colon it could be demonstrated that dihydroxy bile acids (deoxycholate) and diphenolic laxatives (oxyphenisatin) enhance the hydraulic permeability of the mucosal tissue. The permeability changes take place--and there is good experimental evidence--at the zonulae occludentes which bind the epithelial cells together at their luminal borders. Due to laxative action the hydraulic permeability of the colonic mucosa increases to such an extent that according to the Starling forces the normal subepithelial hydrostatic pressure is a sufficient driving force to reverse net sodium, chloride, and water absorption into net secretion. A new concept of "intestinal filtration as a consequence of increased mucosal hydraulic permeability" is proposed to explain the laxative action of deoxycholate and oxyphenisatin in the colon. The question whether inhibition of Na,K-ATPase activity, cyclic AMP-mediated secretion or increased hydraulic permeability of the colonic mucosa are causatively linked to and quantitatively meaningful in intestinal secretion remains open.

Sennoside-induced Secretion is Not Caused by Changes in Mucosal Permeability or Na+,K+-ATPase Activity

“…Nevertheless, an increase in fluid secretion contributes to the laxative effect of sennosides. The secretory effect of many laxatives such as bisacodyl, phenolphthalein, ricinoleic acid, docusate sodium and magnesium sulphate has been associated with damage or inflammation of the intestinal epithelium and an increase in mucosal permeability (Bright-Asare & Binder 1973;Cline et al 1976;Gullikson et al 1977;Wanitschke 1980a;Farack & Nell 1984). Another mechanism proposed is the inhibition of the mucosal N a + , K + -ATPase thereby blocking active Na+ absorption (Rachmilewitz et al 1980;Schreiner et al 1980;Wanitschke 1980b).…”

Net Sodium and Glucose Transport in the Jejunum, Ileum and Colon of Anaesthetized Rats in Response to Intraluminal Theophylline and Anionic Surfactants

“…According to current concepts (Rummel et a/. 1975;Wanitschke 1980) such a change involves an increased leakage at the regions of the tight junctions, thereby causing an augmented paracellular transport. Furthermore, Donowitz & Binder (1975) have shown that the drug may induce increased mucosal formation of CAMP, and have suggested that this may be the main factor in its mode of action.…”

Interaction between Diphenolic Laxatives and Intestinal Bacteria in Vitro

“…These aspects are covered in recent reviews (Rummel et a/. 1975;Binder 1977;Gaginella & Bass 1978;Ewe 1980;Wanitschke 1980). Studies on bacterial interaction with the laxatives have been centered entirely on bacterial enzymatic activity, which is required for hydrolysis of the laxative conjugates and prodrugs when they reach the large intestine.…”