TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells
| Autor: | Katsura Nozawa, Hitoshi Matsushime, Ryosuke Kojima, Toshihide Yokoyama, Yorikata Sano, Hidetsugu Okada, Kohei Inamura, Tomonobu Koizumi, Shinobu Mochizuki, Eri Kawabata-Shoda, Hiroyuki Ito, Hitoshi Doihara |
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| Rok vydání: | 2009 |
| Předmět: |
Ankyrins
Male Serotonin Guinea Pigs Nerve Tissue Proteins Biology Cell Line Transient receptor potential channel Mice Transient Receptor Potential Channels Enterochromaffin Cells Animals Humans Receptor TRPA1 Cation Channel TRPC Cation Channels Gastrointestinal tract Multidisciplinary Biological Sciences Cell biology Rats Biochemistry Gene Expression Regulation Cell culture Enterochromaffin cell Calcium Calcium Channels Gastrointestinal function Gastrointestinal Motility Intracellular |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 106(9) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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