TRPA1 agonists delay gastric emptying in rats through serotonergic pathways. 2009

Hitoshi Doihara, and Katsura Nozawa, and Eri Kawabata-Shoda, and Ryosuke Kojima, and Toshihide Yokoyama, and Hiroyuki Ito
Pharmacology Laboratories, Drug Discovery Research, Astellas Pharma, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. hitoshi.doihara@jp.astellas.com

Our recent study found that TRPA1 is highly expressed in enterochromaffin cells and that stimulation of these cells with TRPA1 agonists enhances 5-hydroxytryptamine (5-HT) secretion in vitro. Here, to demonstrate the 5-HT-releasing effect of TRPA1 agonists in vivo, we examined the effect of TRPA1 agonists on gastric emptying in rats. The results showed that TRPA1 agonists dose-dependently delayed gastric emptying. Further, the effects of TRPA1 agonists on this delay were abolished in rats treated with a TRPA1 antagonist, an inhibitor of tryptophan hydroxylase, or a 5-HT(3) receptor antagonist. Taken together, these results indicate that TRPA1 agonists delay in vivo gastric emptying through serotonergic pathways.

UI MeSH Term Description Entries
D008297 Male Males
D010134 Fenclonine A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin. p-Chlorophenylalanine,para-Chlorophenylalanine,CP-10,188,DL-3-(4-Chlorophenyl)alanine,Fenclonin,Fenclonine (L)-Isomer,Fenclonine Hydrobromide,Fenclonine Hydrochloride,Fenclonine, (D)-Isomer,Hydrobromide, Fenclonine,Hydrochloride, Fenclonine,para Chlorophenylalanine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004759 Enterochromaffin Cells A subtype of enteroendocrine cells found in the gastrointestinal MUCOSA, particularly in the glands of PYLORIC ANTRUM; DUODENUM; and ILEUM. These cells secrete mainly SEROTONIN and some neuropeptides. Their secretory granules stain readily with silver (argentaffin stain). Argentaffin Cells,5-HT-Containing Enterochromaffin Cells,Serotonin-Containing Enterochromaffin Cells,5 HT Containing Enterochromaffin Cells,5-HT-Containing Enterochromaffin Cell,Argentaffin Cell,Cell, Enterochromaffin,Cells, Enterochromaffin,Enterochromaffin Cell,Enterochromaffin Cell, 5-HT-Containing,Enterochromaffin Cell, Serotonin-Containing,Enterochromaffin Cells, 5-HT-Containing,Enterochromaffin Cells, Serotonin-Containing,Serotonin Containing Enterochromaffin Cells,Serotonin-Containing Enterochromaffin Cell
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005746 Gastric Emptying The evacuation of food from the stomach into the duodenum. Emptying, Gastric,Emptyings, Gastric,Gastric Emptyings
D000074025 TRPA1 Cation Channel A highly conserved, non-selective TRP cation channel that contains 14-17 ANKYRIN REPEATS. It functions in cold sensation and NOCICEPTION of endogenous inflammatory factors and volatile irritants. TRPA1 is also activated by CANNABINOIDS and may play a role in sound perception by hair cells of the inner ear. TRPA1 Channel,Transient Receptor Potential Cation Channel Subfamily A, Member 1,Cation Channel, TRPA1,Channel, TRPA1,Channel, TRPA1 Cation
D000171 Acrolein Unsaturated three-carbon aldehyde. 2-Propenal,Acraldehyde,Acrylaldehyde,Acrylic Aldehyde,Allyl Aldehyde,Aqualin,Ethylene Aldehyde,2 Propenal,Aldehyde, Acrylic,Aldehyde, Allyl,Aldehyde, Ethylene
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012430 Ruthenium Red An inorganic dye used in microscopy for differential staining and as a diagnostic reagent. In research this compound is used to study changes in cytoplasmic concentrations of calcium. Ruthenium red inhibits calcium transport through membrane channels. Ammoniated Ruthenium Oxychloride,Oxychloride, Ammoniated Ruthenium,Red, Ruthenium,Ruthenium Oxychloride, Ammoniated

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