Contractile effect of TRPA1 receptor agonists in the isolated mouse intestine

Penuelas, Angelica; Tashima, Kimihito; Tsuchiya, Shizuko; Matsumoto, Kenjiro; Nakamura, Tomonori; Horie, Syunji; Yano, Shingo

doi:10.1016/j.ejphar.2007.08.015

Cited by 85 publications

(80 citation statements)

References 33 publications

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“…TRPA1 immunoreactive fibres were found in the rat MP (Kondo et al, 2009) and mRNA was detected in the isolated smooth muscle layer of rat small intestine ). TRPA1 agonists were furthermore shown to promote contraction of isolated strips of mouse colon (Penuelas et al, 2007). However, mouse colonic compliance did not change by applying mustard oil or after TRPA1 deletion (Cattaruzza et al, 2009).…”

Section: Trpa1mentioning

confidence: 97%

“…TRPM8 mRNA was detected in the fundus (and colon) of rat and was implicated in cooling-induced contractions of fundic muscle strips (Mustafa and Oriowo, 2005). Zhang et al also found TRPM8 mRNA in murine NG, small intestinal and stomach mucosa but Penuelas et al failed to confirm its expression although the same primer pairs were used (Zhang et al, 2004;Penuelas et al, 2007). The latter group also showed that menthol produces slow but long-lasting relaxations of the mouse colon and consequently concluded this phenomenon to be TRPM8-independent (Penuelas et al, 2007).…”

Section: Trpm Channelsmentioning

confidence: 99%

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TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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The members of the superfamily of transient receptor potential (TRP) cation channels are involved in a plethora of cellular functions. During the last decade, a vast amount of evidence is accumulating that attributes an important role to these cation channels in different regulatory aspects of the alimentary tract. In this review we discuss the expression patterns and roles of TRP channels in the regulation of gastrointestinal motility, enteric nervous system signalling and visceral sensation, and provide our perspectives on pharmacological targeting of TRPs as a strategy to treat various gastrointestinal disorders. We found that the current knowledge about the role of some members of the TRP superfamily in neurogastroenterology is rather limited, whereas the function of other TRP channels, especially of those implicated in smooth muscle cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4, TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine cells (TRPM5) is lacking. It is clear that several different TRP channels play important roles in the cellular apparatus that controls gastrointestinal function. They are involved in the regulation of gastrointestinal motility and absorption, visceral sensation and visceral hypersensitivity. TRP channels can be considered as interesting targets to tackle digestive diseases, motility disorders and visceral pain. At present, TRPV1 antagonists are under development for the treatment of heartburn and visceral hypersensitivity, but interference with other TRP channels is also tempting. However, their role in gastrointestinal pathophysiology first needs to be further elucidated.

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Section: Trpa1mentioning

confidence: 97%

Section: Trpm Channelsmentioning

confidence: 99%

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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“…Spontaneous intestinal contractions of circular muscle were recorded as described previously (Penuelas et al, 2007;Boudaka et al, 2009). Briefly, 8-to 12-week-old male WT mice were killed by cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

Mihara¹,

Boudaka²,

Shibasaki³

et al. 2010

J. Neurosci.

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Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (Ͼ52°C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca 2ϩ concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.

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“…In addition, it has been reported that TRPA1 expression and sensitivity are increased under inflammatory conditions in mouse sensory neurons (12, 39). Furthermore, TRPA1 acts as a mechanosensor in the GI tract (11, 28), and mechanical hypersensitivity under inflammatory conditions has been observed in mouse (29) and rat rectal colon (41).TRPA1 expression in colon has been demonstrated by several techniques, including Northern analysis in humans (44) and rats, and dogs (16,42,50). In human and rat duodenum, TRPA1 was found in enterochromaffin cells by in situ hybridization (ISH) (38).…”

mentioning

confidence: 99%

Activation of TRPA1 by luminal stimuli induces EP₄-mediated anion secretion in human and rat colon

Kaji

Yasuoka

Karaki

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kaji I, Yasuoka Y, Karaki S, Kuwahara A. Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon. Am J Physiol Gastrointest Liver Physiol 302: G690-G701, 2012. First published December 29, 2011; doi:10.1152/ajpgi.00289.2011 physiology, anion and fluid secretion is an important function for host defense and is induced by changes in the luminal environment. The transient receptor potential A1 (TRPA1) channel is considered to be a chemosensor in several sensory tissues. Although the function of TRPA1 has been studied in GI motility, its contribution to the transepithelial ion transport system has rarely been discussed. In the present study, we investigated the secretory effect of the potential TRPA1 agonist allyl isothiocyanate (AITC) in rat and human colon using an Ussing chamber. The mucosal application of AITC (10 Ϫ6 -10 Ϫ3 M) induced Cl Ϫ and HCO 3 Ϫ secretion in a concentrationdependent manner, whereas the serosal application induced a significantly weaker effect. AITC-evoked anion secretion was attenuated by tissue pretreatment with piroxicam and prostaglandin (PG) E2; however, this secretion was not affected by TTX, atropine, or extracellular Ca 2ϩ depletion. These experiments indicate that TRPA1 activation induces anion secretion through PG synthesis, independent of neural pathways in the colon. Further analysis also indicates that AITCevoked anion secretion is mediated mainly by the EP4 receptor subtype. The magnitude of the secretory response exhibited segmental heterogeneity in rat colon. Real-time PCR analysis showed the segmental difference was corresponding to the differential expression of EP4 receptor and cyclooxygenase-1 and -2. In addition, RT-PCR, in situ hybridization, and immunohistochemical studies showed TRPA1 expression in the colonic epithelia. Therefore, we conclude that the activation of TRPA1 in colonic epithelial cells is likely involved in the host defense mechanism through rapid anion secretion. colonic chemosensing; prostaglandin E2 THE EPITHELIUM OF THE GASTROINTESTINAL (GI) tract functions not only as a gate for water and nutrients but as a barrier between the luminal and internal environments. Recent studies have suggested that luminal sensory molecules in the small intestine influence nutrient metabolism and local physiological responses (1, 31, 32). Molecular identification of sensory receptors, such as olfactory, taste, and thermo-receptors, which are part of the transient receptor potential (TRP) family, has helped to elucidate chemical-sensing systems that detect the luminal state. However, the physiological roles of these receptors in colonic ion transport have rarely been investigated at the organ level. In particular, transepithelial anion secretion followed by fluid secretion is regulated by diverse systems, including the nervous, endocrine, and immune systems (4, 17), and is considered an important function for host defense. Therefore, experiments at the tissue or organ levels are important for understanding the contribution of ...

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Contractile effect of TRPA1 receptor agonists in the isolated mouse intestine

Cited by 85 publications

References 33 publications

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

Activation of TRPA1 by luminal stimuli induces EP₄-mediated anion secretion in human and rat colon

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