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TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells
Open accessAbstract
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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“TRPA1 can promote serotonin release from enterochromaffin cells and subsequently increase colonic peristalsis and tone [35, 36].”
From The effects of ginger supplementation on common gastrointestinal symptoms in patients with relapsing-remitting multiple sclerosis: a double-blind randomized placebo-controlled trial (2023) · cites this paper as [35]
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Wen, C., Yan, W., Mai, C., Duan, Z., Zheng, J., Sun, C., & Yang, N. (2021) · Figshare · doi:10.6084/m9.figshare.14715100
Wen, C., Yan, W., Mai, C., Duan, Z., Zheng, J., Sun, C., & Yang, N. (2021) · Figshare · doi:10.6084/m9.figshare.14715076
Al‐Okbi, S. Y., Mohammed, S. E., Al-Siedy, E. S. K., Shalaby, S. I., & Mohamed, D. A. (2026) · Journal of Food Biochemistry · doi:10.1155/jfbc/2198770
Yang, Q., Wang, Y.-L., Leng, Y., Lin, E., Guo, M., Chen, L.-X., & Li, H. (2026) · Journal of Agriculture and Food Research · doi:10.1016/j.jafr.2026.102926
Metadata
- 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
- 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
- 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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