TRPA1 agonists delay gastric emptying in rats through serotonergic pathways

Doihara, Hitoshi; Nozawa, Katsura; Kawabata-Shoda, Eri; Kojima, Ryosuke; Yokoyama, Toshihide; Ito, Hiroyuki

doi:10.1007/s00210-009-0435-7

Cited by 59 publications

(49 citation statements)

References 26 publications

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“…Furthermore, a subtype of enteroendocrine cells has been shown to express abundant TRPA1 whose stimulation induces 5-HT release that can activate intrinsic nerves and vagal endings (39). These reports strongly suggest that TRPA1 may play a role in the regulation of gut motility as confirmed by several motility studies of experimental animals using TRPA1 ligands and gene-manipulation (11,12,26,42,43). More recently, considerable attention has been given to the presence of TRPA1 in IE cells.…”

Section: Discussionmentioning

confidence: 86%

Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

Kono

Kaneko

Omiya

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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. TU-100 contains multiple TRP activators. In the present study, therefore, we examined the involvement of TRP channels in the ADM-mediated vasodilatatory effect of TU-100. Rats were treated intraduodenally with the TRP vanilloid type 1 (TRPV1) agonist capsaicin (CAP), the TRP ankyrin 1 (TRPA1) agonist allyl-isothiocyanate (AITC), or TU-100, and jejunum IBF was evaluated using laser-Doppler blood flowmetry. All three compounds resulted in vasodilatation, and the vasodilatory effect of TU-100 was abolished by a TRPA1 antagonist but not by a TRPV1 antagonist. Vasodilatation induced by AITC and TU-100 was abrogated by anti-ADM antibody treatment. RT-PCR and flow cytometry revealed that an IEC-6 cell line originated from the small intestine and purified IE cells expressed ADM and TRPA1 but not TRPV1. AITC increased ADM release in IEC cells remarkably, while CAP had no effect. TU-100 and its ingredient 6-shogaol (6SG) increased ADM release dose-dependently, and the effects were abrogated by a TRPA1 antagonist. 6SG showed similar TRPA1-dependent vasodilatation in vivo. These results indicate that TRPA1 in IE cells may play an important role in controlling bowel microcirculation via ADM release. Epithelial TRPA1 appears to be a promising target for the development of novel strategies for the treatment of various gastrointestinal disorders.daikenchuto; TU-100; vasodilatation; 6-shogaol; inflammatory bowel diseases TRANSIENT RECEPTOR POTENTIAL (TRP) channels are nonselective calcium ion channels ubiquitously expressed in many tissues and are known to participate in a broad range of physical, chemical, and environmental stimuli such as taste, temperature, changes in osmolarity, pressure, stretch, and light.

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Section: Discussionmentioning

confidence: 86%

Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

Kono

Kaneko

Omiya

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…TRPA1 was reported to be expressed in different mammalian tissues, including brain, intestine and pancreas (76, 77), human skin keratinocytes (78, 79), and vestibular and auditory sensory epithelia (78, 80). However, functional activity of TRPA1 channels is most consistently characterized in sensory neurons and other cells with sensory functions.…”

Section: Discussionmentioning

confidence: 99%

TRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis

et al. 2013

The Journal of Immunology

171

172

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Chronic debilitating pruritus is a cardinal feature of a topic dermatitis (AD). Little is known about the underlying mechanisms. Antihistamines lack efficacy in treating itch in AD, suggesting the existence of histamine-independent itch pathways in AD. Transient receptor potential ankyrin 1 (TRPA1) is essential in the signaling pathways that promote histamine-independent itch. In the present study, we tested the hypothesis that TRPA1-dependent neural pathways play a key role in chronic itch in AD using an IL-13 transgenic mouse model of AD. In these mice, IL-13 causes chronic AD characterized by intensive chronic itch associated with markedly enhanced growth of dermal neuropeptide-secreting afferent nerve fibers and enhanced expression of TRPA1 in dermal sensory nerve fibers, their dorsal root ganglia, and mast cells. Inhibition of TRPA1 with a specific antagonist in these mice selectively attenuated itch-evoked scratching. Genetic deletion of mast cells in these mice led to significantly diminished itch-scratching behaviors and reduced TRPA1 expression in dermal neuropeptide containing afferents in the AD skin. Interestingly, IL-13 strongly stimulates TRPA1 expression, which is functional in calcium mobilization in mast cells. In accordance with these observations in the AD mice, TRPA1 expression was highly enhanced in the dermal afferent nerves, mast cells, and the epidermis in the lesional skin biopsies from patients with AD, but not in the skin from normal subjects. These studies demonstrate a novel neural mechanism underlying chronic itch in AD and highlight the complex interactions among TRPA1+ dermal afferent nerves and TRPA1+ mast cells in a Th2-dominated inflammatory environment.

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“…Dietary cinnamaldehyde has been shown to effect the function of the gastrointestinal tract including gut motility (78), gastric emptying (79), and cholecystokinin secretion. A recent finding investigated the effect of TRPA1 on ghrelin secretion (44).…”

Section: Trpv1 Trpa1 and Secretion Of Ghrelin And Glucagon-like Peptmentioning

confidence: 99%

Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity

Derbenev

Zsombok

2015

Semin Immunopathol

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Diabetes mellitus and obesity, which is a major risk factor in the development of type 2 diabetes mellitus, have reached epidemic proportions worldwide including the United States. The current statistics and forecasts, both short- and long-term, are alarming and predict severe problems in the near future. Therefore, there is a race for developing new compounds, discovering new receptors or finding alternative solutions to prevent and/or treat the symptoms and complications related to obesity and diabetes mellitus. It is well demonstrated that members of the transient receptor potential (TRP) superfamily play a crucial role in a variety of biological functions both in health and disease. In the recent years, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) were shown to have beneficial effects on whole body metabolism including glucose homeostasis. TRPV1 and TRPA1 have been associated with control of weight, pancreatic function, hormone secretion, thermogenesis and neuronal function; which suggest a potential therapeutic value of these channels. This review summarizes recent findings regarding TRPV1 and TRPA1 in association with whole body metabolism with emphasis on obese and diabetic conditions.

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TRPA1 agonists delay gastric emptying in rats through serotonergic pathways

Cited by 59 publications

References 26 publications

Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

TRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis

Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity

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