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TRPA1 agonists delay gastric emptying in rats through serotonergic pathways
Hitoshi Doihara1, Katsura Nozawa, Eri Kawabata-Shoda
1Pharmacology Laboratories, Drug Discovery Research, Astellas Pharma, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. hitoshi.doihara@jp.astellas.com
Naunyn-Schmiedeberg'S Archives of Pharmacology
|July 25, 2009
Summary
TRPA1 agonists delay gastric emptying in rats by influencing serotonin pathways. Blocking TRPA1 or serotonin production/receptors reversed this effect, confirming the mechanism.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Pharmacology
Background:
- Transient Receptor Potential Ankyrin 1 (TRPA1) channels are expressed in enterochromaffin (EC) cells.
- TRPA1 activation in vitro stimulates 5-hydroxytryptamine (5-HT) secretion from EC cells.
Purpose of the Study:
- To investigate the in vivo effect of TRPA1 agonists on gastric emptying.
- To elucidate the role of serotonergic pathways in TRPA1-mediated gastric motility regulation.
Main Methods:
- Administration of TRPA1 agonists to rats to assess gastric emptying.
- Utilized TRPA1 antagonists, tryptophan hydroxylase inhibitors, and 5-HT(3) receptor antagonists to probe the mechanism.
Main Results:
- TRPA1 agonists caused a dose-dependent delay in gastric emptying.
- This delay was significantly attenuated by TRPA1 antagonists and inhibitors of the serotonergic pathway.
Conclusions:
- TRPA1 agonists delay gastric emptying in vivo.
- This effect is mediated through activation of serotonergic pathways involving 5-HT secretion and 5-HT(3) receptors.
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