Secretory effects of a luminal bitter tastant and expressions of bitter taste receptors, T2Rs, in the human and rat large intestine.
Taste transduction molecules, such as Galpha(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-n-propyl-2-thiouracil (6-PTU), on transepithelial ion transport was investigated using the Ussing chamber technique. In mucosal-submucosal preparations, mucosal 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.
Kaji
Izumi
I
Laboratory of Physiology, Graduate School of Nutrition and Environmental Sciences, Institute for Environmental Science, University of Shizuoka, Shizuoka, Japan.
Karaki
Shin-ichiro
S
Fukami
Yasuyuki
Y
Terasaki
Masaki
M
Kuwahara
Atsukazu
A
D000368:Aged; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007419:Intestinal Secretions / Q000187:drug effects*; D007420:Intestine, Large / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D010894:Piroxicam / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D000098706:Taste Receptors, Type 2
D001639:Bicarbonates; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D026941:Sodium Channel Blockers; D000098706:Taste Receptors, Type 2; D010894:Piroxicam; D013779:Tetrodotoxin; D011441:Propylthiouracil; D015232:Dinoprostone