Organic acid proton donors decrease intestinal secretion caused by enterotoxins

The effects of several weak acids on the secretory actions of cholera toxin and the heat-stable enterotoxin of Escherichia coli (ST) have been examined in ligated jejunal loops in weanling pigs. Ascorbic and acetic acids had no effect, but L-lactic acid reduced the net fluid secretion caused by cholera toxin. Glutaric acid and p-aminobenzoic acid blocked net fluid secretion caused by cholera toxin or by ST. Antisecretory effects were pH dependent for p-aminobenzoic acid in this study and for nicotinic acid in a previous report (6). At a pH of 5.0, p-aminobenzoic acid treatment increased lumen-to-blood sodium flux and decreased the blood-to-lumen sodium flux caused by cholera toxin. These weak acid effects were more marked on fluid fluxes in enterotoxin-treated loops than in control loops and persisted for 20-30 min after acid removal from loops. These findings are discussed in terms of requirements for antisecretory activity and possible modes of action of antisecretory compounds.