Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels

Nagatomo, Katsuhiro; Kubo, Yoshihiro

doi:10.1073/pnas.0809769105

Cited by 107 publications

(77 citation statements)

References 35 publications

(44 reference statements)

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“…Another group failed to record any coldinduced activity of recombinant rat TRPA1 (rTRPA1) but demonstrated that rTRPA1 was activated by the pungent compound allyl isothiocyanate (AITC, also known as mustard oil) and by Δ 9 -tetrahydrocannabinol, the active compound of marijuana (Jordt et al 2004). A plethora of chemical agonists of TRPA1 were subsequently discovered, including pungent compounds such as cinnamaldehyde, methyl salicylate, allicin (from garlic), acrolein (2-propenal, from exhaust smoke), sesquiterpenes, caffeine, and inflammatory mediators (bradykinin, NO, A-, and J-series prostaglandins) (Bandell et al 2004;Bautista et al 2005Bautista et al , 2006Escalera et al 2008;Nagatomo and Kubo 2008;Takahashi et al 2008;Taylor-Clark et al 2008). Even menthol was shown to have a bimodal action on TRPA1, as it activates the channel at low-micromolar concentrations and blocks it at higher ones (Karashima et al 2007).…”

Section: Trpa1 As a Sensor For Noxious Coldmentioning

confidence: 99%

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Babeș

2009

Biophys Rev

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Substantial progress in understanding thermal transduction in peripheral sensory nerve endings was achieved with the recent cloning of six thermally gated ion channels from the TRP (transient receptor potential) super-family. Two of these channels, TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1), are expressed in dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons, are activated by various degrees of cooling, and are candidates for mediating gentle cooling and noxious cold, respectively. However, accumulating evidence suggests that more than just these two channels are involved in cold sensing in mammals. A recent report described a critical role of the voltage-gated tetrodotoxin-resistant sodium channel Na v 1.8 in perceiving intense cold and noxious stimuli at cold temperatures. Other ion channels, such as two-pore domain background potassium channels (K2P), are known to be expressed in peripheral nerves, have pronounced temperature dependence, and may contribute to cold sensing and/or cold hypersensitivity in pain states. This article reviews the evidence supporting a role for each of these channels in cold transduction, focusing on their biophysical properties, expression pattern, and modulation by pro-inflammatory mediators.

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Section: Trpa1 As a Sensor For Noxious Coldmentioning

confidence: 99%

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Babeș

2009

Biophys Rev

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“…These observations suggest that TRPA1 functions as a luminal chemosensor. Moreover, the response to AITC, a main pungent compound in radish and wasabi, was lost in neurons taken from TRPA1-deficient mice (8,37), indicating that AITC is a specific TRPA1 agonist. AITC has been used to study gastrointestinal motility: it induces longitudinal muscle contraction in isolated mouse colon through the TTX-sensitive neural pathway (42) and causes gastrointestinal contraction in conscious dogs (16).…”

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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“…Menthol activates hTRPA1 (Xiao et al, 2008) but has a bimodal action at mouse TRPA1 (mTRPA1) that can lead to channel block at high concentrations (Karashima et al, 2009). Caffeine is an agonist at mTRPA1 but an antagonist at hTRPA1 (Nagatomo and Kubo, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Reactive TRPA1 agonists consist of endogenous ligands, such as 4-hydroxynonenal (4-HNE) (Macpherson et al, 2007;Trevisani et al, 2007) and 15-deoxy-prostaglandin J 2 (15-d-PGJ 2 ) (Cruz-Orengo et al, 2008;Maher et al, 2008), and pungent natural products, such as mustard oil (MO) (Jordt et al, 2004), cinnamaldehyde (CA) (Bandell et al, 2004), and allicin (Bautista et al, 2005;Macpherson et al, 2005). Nonreactive TRPA1 agonists are a diverse group of ligands that include amphipathic molecules [e.g., trinitrophenol (TNP)] (Hill and Schaefer, 2007), lipids [e.g., farnesyl thiosalicylic acid (FTS)] (Maher et al, 2008), and pharmacological agents [e.g., menthol, caffeine, and 3Ј-carbamoylbiphenyl-3-yl cyclohexylcarbamate (URB597)] Nagatomo and Kubo, 2008;Xiao et al, 2008;Karashima et al, 2009). Some of these, such as menthol and caffeine, display species-specific differential pharmacology at TRPA1.…”

Section: Introductionmentioning

confidence: 99%

Species Comparison and Pharmacological Characterization of Human, Monkey, Rat, and Mouse TRPA1 Channels

Bianchi

Zhang²,

Reilly³

et al. 2012

J Pharmacol Exp Ther

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The transient receptor potential ankyrin-1 (TRPA1) channel has emerged as an attractive target for development of analgesic and anti-inflammatory drugs. However, drug discovery efforts targeting TRPA1 have been hampered by differences between human and rodent species. Many compounds have been identified to have antagonist activity at human TRPA1 (hTRPA1), but when tested at rat TRPA1 (rTRPA1) and mouse TRPA1 (mTRPA1), they show reduced potency as antagonists, no effect, or agonist activity. These compounds are excluded from further drug development because they cannot be tested in preclinical studies using conventional rat/mouse models. To broaden our understanding of species-specific differences, we cloned and functionally characterized rhesus monkey TRPA1 (rhTRPA1) and compared its pharmacological profile to hTRPA1, rTRPA1, and mTRPA1 channels. The functional activities of a diverse group of TRPA1 ligands (both reactive and nonreactive) were determined in a fluorescent Ca 2ϩ influx assay, using transiently transfected human embryonic kidney 293-F cells. 4-Methyl-N-[2,2,2-trichloro-1-(4-nitro-phenylsulfanyl)-ethyl]-benzamide, menthol, and caffeine displayed species-specific differential pharmacology at TRPA1. The pharmacological profile of the rhTRPA1 channel was found to be similar to the hTRPA1 channel. In contrast, the rTRPA1 and mTRPA1 channels closely resembled each other but were pharmacologically distinct from either hTRPA1 or rhTRPA1 channels. Our findings reveal that TRPA1 function differs between primate and rodent species and suggest that rhesus monkey could serve as a surrogate species for humans in preclinical studies.

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Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels

Cited by 107 publications

References 35 publications

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

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

Species Comparison and Pharmacological Characterization of Human, Monkey, Rat, and Mouse TRPA1 Channels

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