title: TRPA1 agonists delay gastric emptying in rats through serotonergic pathways.
abstract: 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.
authors.affiliation: Pharmacology Laboratories, Drug Discovery Research, Astellas Pharma, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. hitoshi.doihara@jp.astellas.com
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Doihara
authors.forename: Katsura
authors.initials: K
authors.lastname: Nozawa
authors.forename: Eri
authors.initials: E
authors.lastname: Kawabata-Shoda
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kojima
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017487:Ankyrins; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D017829:Granisetron / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000171:Acrolein; D017487:Ankyrins; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010134:Fenclonine; D017829:Granisetron; D017879:Isothiocyanates; D044406:Receptors, Serotonin, 5-HT3; D012430:Ruthenium Red; D012701:Serotonin; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D014365:Tryptophan Hydroxylase; C480976:Trpa1 protein, rat; C004471:allyl isothiocyanate; C012843:cinnamaldehyde