Interaction of laxatives with enzymes of cyclic AMP metabolism from human colonic mucosa.
The mechanism by which laxatives such as dioctyl sodium sulfosuccinate and ricinoleic acid evoke colonic fluid secretion has been suggested to involve mucosal cyclic AMP. Ricinoleic acid and dioctyl sodium sulfosuccinate were tested for their capacity to modulate the key enzymes of cAMP-metabolism--adenylate cyclase and cAMP-phosphodiesterase--in human colonic mucosa. Both laxatives were ineffective stimuli of human colonic adenylate cyclase. In contrast to ricinoleic acid, dioctyl sodium sulfosuccinate was a competitive inhibitor of soluble cAMP-phosphodiesterase activity. These experiments suggest that the cathartic properties of dioctyl sodium sulfosuccinate in human colonic mucosa might be mediated by cyclic AMP via inhibition of soluble phosphodiesterase activity.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000494:pharmacology; D002400:Cathartics / Q000494:pharmacology*; D003106:Colon / Q000201:enzymology*; D004143:Dioctyl Sulfosuccinic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D012277:Ricinoleic Acids / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D001647:Bile Acids and Salts; D002400:Cathartics; D012277:Ricinoleic Acids; D004143:Dioctyl Sulfosuccinic Acid; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases