TRPA1 agonists delay gastric emptying in rats through serotonergic pathways.
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.
Doihara
Hitoshi
H
Pharmacology Laboratories, Drug Discovery Research, Astellas Pharma, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. hitoshi.doihara@jp.astellas.com
Nozawa
Katsura
K
Kawabata-Shoda
Eri
E
Kojima
Ryosuke
R
Yokoyama
Toshihide
T
Ito
Hiroyuki
H
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
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