Secretory effects of a luminal bitter tastant and expressions of bitter taste receptors, T2Rs, in the human and rat large intestine

摘要

Taste transduction molecules, such as Gα_(gust), and taste receptor families for bitter [taste receptor type 2 (T2R)], sweet, and umami, have previously been identified in taste buds and the gastrointestinal (GI) tract; however, their physiological functions in GI tissues are still unclear. Here, we investigated the physiological function and expression of T2R in human and rat large intestine using various physiological and molecular biological techniques. To study the physiological function of T2R, the effect of a bitter compound, 6-/i-propyl-2-thiouracil (6-PTU), on transepithelial ion transport was investigated using the Ussing chamber technique. In mucosal-submucosal preparations, mu-cosal 6-PTU evoked Cl~- and (HCO_3)~- secretions in a concentration-dependent manner. In rat middle colon, levels of 6-PTU-evoked anion secretion were higher than in distal colon, but there was no such difference in human large intestine. The response to 6-PTU was greatly reduced by piroxicam, but not by tetrodotoxin. Additionally, prostaglandin E_2 concentration-dependently potentiated the response to 6-PTU. Transcripts of multiple T2Rs (putative 6-PTU receptors) were detected in both human and rat colonic mucosa by RT-PCR. In conclusion, these results suggest that the T2R ligand, 6-PTU, evokes anion secretion, and such response is regulated by prostaglandins. This luminal bitter sensing mechanism may be important for host defense in the GI tract.