In particular, transepithelial anion secretion followed by fluid secretion is regulated by diverse systems, including the nervous, endocrine, and immune systems ( 4, 17), and is considered an important function for host defense. However, the physiological roles of these receptors in colonic ion transport have rarely been investigated at the organ level. Molecular identification of sensory receptors, such as olfactory, taste, and thermo-receptors, which are part of the transient receptor potential (TRP) family, has helped to elucidate chemical-sensing systems that detect the luminal state. Recent studies have suggested that luminal sensory molecules in the small intestine influence nutrient metabolism and local physiological responses ( 1, 31, 32). The epithelium of the gastrointestinal (GI) tract functions not only as a gate for water and nutrients but as a barrier between the luminal and internal environments. Therefore, we conclude that the activation of TRPA1 in colonic epithelial cells is likely involved in the host defense mechanism through rapid anion secretion. In addition, RT-PCR, in situ hybridization, and immunohistochemical studies showed TRPA1 expression in the colonic epithelia. Real-time PCR analysis showed the segmental difference was corresponding to the differential expression of EP 4 receptor and cyclooxygenase-1 and -2. The magnitude of the secretory response exhibited segmental heterogeneity in rat colon. Further analysis also indicates that AITC-evoked anion secretion is mediated mainly by the EP 4 receptor subtype. These experiments indicate that TRPA1 activation induces anion secretion through PG synthesis, independent of neural pathways in the colon. AITC-evoked anion secretion was attenuated by tissue pretreatment with piroxicam and prostaglandin (PG) E 2 however, this secretion was not affected by TTX, atropine, or extracellular Ca 2+ depletion. The mucosal application of AITC (10 −6-10 −3 M) induced Cl − and HCO 3 − secretion in a concentration-dependent manner, whereas the serosal application induced a significantly weaker effect.
In the present study, we investigated the secretory effect of the potential TRPA1 agonist allyl isothiocyanate (AITC) in rat and human colon using an Ussing chamber. Although the function of TRPA1 has been studied in GI motility, its contribution to the transepithelial ion transport system has rarely been discussed. The transient receptor potential A1 (TRPA1) channel is considered to be a chemosensor in several sensory tissues. In gastrointestinal (GI) physiology, anion and fluid secretion is an important function for host defense and is induced by changes in the luminal environment.
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