We tested the hypothesis that
5-aminosalicylic acid (5-ASA) inhibits toxin A-induced generation of colonic
leukotriene B4 (
LTB4) and toxin A
colitis in rats. Isolated colonic segments in anesthetized rats were treated intraluminally with toxin A for 3 hours with or without 30 minutes of pretreatment with either 5-ASA or
sulfapyridine and then colonic tissue levels of
LTB4 were measured and
inflammation was assessed. Separately,
sulfasalazine was administered to rats in their
drinking water for 5 days, isolated colonic segments were then prepared, toxin A was administered, and
inflammation was assessed as before. Pretreatment with 5-ASA inhibited toxin A-induced increased tissue
LTB4 concentration in the colon.
Sulfasalazine and 5-ASA but not
sulfapyridine significantly inhibited toxin A
colitis. However, pretreatment with 5-ASA did not protect against direct TRPV1-mediated
colitis caused by
capsaicin. Toxin A stimulated the release of
substance P (SP), and this effect was also inhibited by
sulfasalazine and 5-ASA but not by
sulfapyridine. Thus, toxin A stimulates colonic
LTB4 resulting in activation of TRPV1, release of SP, and
colitis. Inhibition of 5-LO by 5-ASA disrupts this pathway and supports the concept that
LTB4 activation of TRPV1 plays a role in toxin A
colitis.