TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells.
Serotonin (5-hydroxytryptamine; 5-HT) is abundantly present throughout the gastrointestinal tract and stored mostly in enterochromaffin (EC) cells, which are located on the mucosal surface. 5-HT released from EC cells stimulate both intrinsic and extrinsic nerves, which results in various physiological and pathophysiological responses, such as gastrointestinal contractions. EC cells are believed to have the ability to respond to the chemical composition of the luminal contents of the gut; however, the underlying molecular and cellular mechanisms have not been identified. Here, we demonstrate that the transient receptor potential (TRP) cation channel TRPA1, which is activated by pungent compounds or cold temperature, is highly expressed in EC cells. We also found that TRPA1 agonists, including allyl isothiocyanate and cinnamaldehyde, stimulate EC cell functions, such as increasing intracellular Ca(2+) levels and 5-HT release, by using highly concentrated EC cell fractions and a model of EC cell function, the RIN14B cell line. Furthermore, we showed that allyl isothiocyanate promotes the contraction of isolated guinea pig ileum via the 5-HT(3) receptor. Taken together, our results indicate that TRPA1 acts as a sensor molecule for EC cells and may regulate gastrointestinal function.
Nozawa
Katsura
K
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. katsura.nozawa@jp.astellas.com
Kawabata-Shoda
Eri
E
Doihara
Hitoshi
H
Kojima
Ryosuke
R
Okada
Hidetsugu
H
Mochizuki
Shinobu
S
Sano
Yorikata
Y
Inamura
Kohei
K
Matsushime
Hitoshi
H
Koizumi
Tomonobu
T
Yokoyama
Toshihide
T
Ito
Hiroyuki
H
D000818:Animals; D017487:Ankyrins; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004759:Enterochromaffin Cells / Q000378:metabolism*; D005769:Gastrointestinal Motility; D005786:Gene Expression Regulation / Q000235:genetics; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*
D017487:Ankyrins; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C480976:Trpa1 protein, rat; D012701:Serotonin; D002118:Calcium