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Organic acid proton donors decrease intestinal secretion caused by enterotoxins

G W Forsyth, R A Kapitany, D L Hamilton

The American Journal of Physiology

|September 1, 1981

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Certain weak acids, like glutaric and p-aminobenzoic acid, can block intestinal fluid secretion caused by cholera toxin and E. coli heat-stable enterotoxin (ST) in pigs.

Area of Science:

Gastroenterology
Microbiology
Pharmacology

Background:

Cholera toxin and E. coli heat-stable enterotoxin (ST) cause significant intestinal fluid secretion.
Understanding factors that modulate these secretory actions is crucial for developing treatments.

Purpose of the Study:

To investigate the antisecretory effects of various weak acids on cholera toxin and ST-induced intestinal fluid secretion in a piglet model.

Main Methods:

Ligated jejunal loops in weanling pigs were used to assess fluid and ion fluxes.
Exposure to cholera toxin, ST, and different weak acids (ascorbic, acetic, L-lactic, glutaric, p-aminobenzoic, nicotinic) was performed.
pH-dependency of antisecretory effects was evaluated.

Main Results:

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L-lactic acid partially reduced cholera toxin-induced fluid secretion.
Glutaric acid and p-aminobenzoic acid effectively blocked fluid secretion induced by both cholera toxin and ST.
Antisecretory effects of p-aminobenzoic acid were pH-dependent and influenced sodium flux.
These effects persisted after acid removal.

Conclusions:

Specific weak acids, notably glutaric and p-aminobenzoic acid, demonstrate significant antisecretory potential against bacterial enterotoxins.
The findings suggest potential therapeutic applications for weak acids in managing toxin-mediated diarrheal diseases.
Further research into the mechanisms of action and optimal conditions for antisecretory activity is warranted.