TRPA1 agonists delay gastric emptying in rats through serotonergic pathways

被引：59

作者：

Doihara, Hitoshi ^{[1
]}

Nozawa, Katsura ^{[1
]}

Kawabata-Shoda, Eri ^{[1
]}

Kojima, Ryosuke ^{[1
]}

Yokoyama, Toshihide ^{[1
]}

Ito, Hiroyuki ^{[1
]}

机构：

[1] Astellas Pharma, Pharmacol Labs, Drug Discovery Res, Tsukuba, Ibaraki, Japan

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 2009年 / 380卷 / 04期

关键词：

TRPA1; Gastric emptying; 5-HT; MAST-CELL; GASTROINTESTINAL MOTILITY; ENTEROCHROMAFFIN CELLS; CHANNEL; COLD; PAIN; GUT; DESENSITIZATION; ACTIVATION; DISORDERS;

D O I：

10.1007/s00210-009-0435-7

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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-HT3 receptor antagonist. Taken together, these results indicate that TRPA1 agonists delay in vivo gastric emptying through serotonergic pathways.

引用

页码：353 / 357

页数：5

共 26 条

[1]

Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization [J].

Akopian, Armen N. ;

Ruparel, Nikita B. ;

Jeske, Nathaniel A. ;

Hargreaves, Kenneth M. .

JOURNAL OF PHYSIOLOGY-LONDON, 2007, 583 (01) :175-193

[2]

Pronociceptive response elicited by TRPA1 receptor activation in mice [J].

Andrade, E. L. ;

Luiz, A. P. ;

Ferreira, J. ;

Calixto, J. B. .

NEUROSCIENCE, 2008, 152 (02) :511-520

[3]

The role of medial hypothalamic serotonin in the suppression of feeding in a rat model of colitis [J].

Ballinger, A ;

El-Haj, T ;

Perrett, D ;

Turvill, J ;

Obeid, O ;

Dryden, S ;

Williams, G ;

Farthing, MJG .

GASTROENTEROLOGY, 2000, 118 (03) :544-553

[4]

Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin [J].

Bandell, M ;

Story, GM ;

Hwang, SW ;

Viswanath, V ;

Eid, SR ;

Petrus, MJ ;

Earley, TJ ;

Patapoutian, A .

NEURON, 2004, 41 (06) :849-857

[5]

Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation [J].

Bang, Sangsu ;

Kim, Kyung Yoon ;

Yoo, Sungjae ;

Kim, Yoon Gyoon ;

Hwang, Sun Wook .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2007, 26 (09) :2516-2523

[6]

TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents [J].

Bautista, DM ;

Jordt, SE ;

Nikai, T ;

Tsuruda, PR ;

Read, AJ ;

Poblete, J ;

Yamoah, EN ;

Basbaum, AI ;

Julius, D .

CELL, 2006, 124 (06) :1269-1282

[7]

Enterochromaffin cells of the human gut: Sensors for spices and odorants [J].

Braun, Thomas ;

Voland, Petra ;

Kunz, Lars ;

Prinz, Christian ;

Gratzl, Manfred .

GASTROENTEROLOGY, 2007, 132 (05) :1890-1901

[8]

TRP channels and pain [J].

Cortright, Daniel N. ;

Krause, James E. ;

Broom, Daniel C. .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2007, 1772 (08) :978-988

[9]

Plasticity in serotonin control mechanisms in the gut [J].

Gershon, MD .

CURRENT OPINION IN PHARMACOLOGY, 2003, 3 (06) :600-607

[10]

The serotonin signaling system: From basic understanding to drug development-for functional GI disorders [J].

Gershon, Michael D. ;

Tack, Jan .

GASTROENTEROLOGY, 2007, 132 (01) :397-414

← 1 2 3 →