Cited by 413Ion Channels and ReceptorsGastrointestinal motility and disordersBiochemical Analysis and Sensing Techniques

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TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

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Nozawa, Katsura, Kawabata-Shoda, Eri, Doihara, Hitoshi, Kojima, Ryosuke, Okada, Hidetsugu, Mochizuki, Shinobu, Sano, Yorikata, Inamura, Kohei, Matsushime, Hitoshi, Koizumi, Tomonobu, Yokoyama, Toshihide, Ito, Hiroyuki·2009·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0805323106PMC PMC2651261

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Abstract

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.

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Authors: Nozawa, K., Kawabata-Shoda, E., Doihara, H., Kojima, R., Okada, H., Mochizuki, S., Sano, Y., Inamura, K., Matsushime, H., Koizumi, T., Yokoyama, T., & Ito, H.
Affiliations: Astellas Pharma (Japan) (JP)
Corresponding author: Nozawa, Katsura
ORCID: Koizumi, Tomonobu
Ito, Hiroyuki
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2009-03-03
Volume: 106
Issue: 9
Pages: 3408-3413
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0805323106
PMC: PMC2651261
OpenAlex: W2156291426
Cited by: 399
References: 49
Citations by year: 2026: 16 · 2025: 32 · 2024: 20 · 2023: 31 · 2022: 25 · 2021: 46 · 2020: 18 · 2019: 23 · 2018: 24 · 2017: 21 · 2016: 24 · 2015: 15 · 2014: 21 · 2013: 24 · 2012: 21
FWCI: 9.74
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
Keywords: TRPA1, enterochromaffin cells, serotonin release, gastrointestinal motility, allyl isothiocyanate, cinnamaldehyde, 5-HT3 receptor, ileal contraction, intracellular calcium, sensory transduction
MeSH terms: TRPA1 Cation Channel, Animals, Calcium, Cell Line, Enterochromaffin Cells, Gastrointestinal Motility, Gene Expression Regulation, Guinea Pigs, Humans, Male, Nerve Tissue Proteins, Serotonin, Calcium Channels, Ankyrins, Transient Receptor Potential Channels, TRPC Cation Channels, Mice, Rats

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TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

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