Intestinal filtration as a consequence of increased mucosal hydraulic permeability. A new concept for laxative action.
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.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002400:Cathartics / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology; D004563:Electrochemistry; D005374:Filtration; D007413:Intestinal Mucosa / Q000187:drug effects*; D010114:Oxyphenisatin Acetate / Q000494:pharmacology; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism
D002400:Cathartics; D003840:Deoxycholic Acid; D012964:Sodium; D000251:Adenosine Triphosphatases; D011188:Potassium; D010114:Oxyphenisatin Acetate