Abstract
The transient receptor potential A1 (TRPA1) channel is considered a chemosensor in several sensory tissues. In the present study, we investigated the secretory effect of potential TRPA1 agonist allyl isothiocyanate (AITC) in rat and human colons using the Ussing flux chamber. The mucosal application of AITC (10−6–10−3 M) induced Cl− and HCO3 − secretion in a concentration‐dependent manner, while the serosal application induced weaker effect. AITC‐evoked anion secretion was attenuated by the pretreatment with cyclooxygenase inhibitor piroxicam and prostaglandin (PG) E2, but the secretion was not affected by tetrodotoxin, atropine, or extracellular Ca2+ depletion. These results indicated that TRPA1 activation induces anion secretion through PG synthesis independent of neural pathway in the colon. Further analysis also indicated that AITC‐evoked anion secretion is mainly mediated by EP4. In addition, RT‐PCR using isolated colonic crypts, in situ hybridization and immunohistochemistry supported the TRPA1 expression in epithelial cells. Therefore, we conclude that the activation of TRPA1 activity on the colonic epithelial cells is likely involved in host defense mechanism through rapid anion secretion.
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