How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways

Simon, Sidney A.; Liedtke, Wolfgang

doi:10.1172/jci36111

Cited by 40 publications

(45 citation statements)

References 26 publications

(32 reference statements)

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“…7D). Given that of the two other VA-sensitive TRP members, TRPV1 is not expressed in these neurons and TRPA1 is not sensitive to capsazepine Cornett et al, 2008;Eilers et al, 2010), this provides additional confirmation of the involvement of TRPM8 in the observed effects (Simon and Liedtke, 2008). Moreover, as in HEK M8 cells, prolonged exposure of mentholresponding DRG neurons to halothane after the initial current activation, caused pronounced current inhibition (Fig.…”

Section: Modulation By Vas Of Endogenous Trpm8 In Drg Neuronssupporting

confidence: 56%

Complex modulation of the cold receptor TRPM8 by volatile anaesthetics and its role in complications of general anaesthesia

Abeele

Kondratskyi

Dubois

et al. 2013

Journal of Cell Science

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SummaryThe mechanisms by which volatile general anaesthetics (VAs) produce a depression of central nervous system are beginning to be better understood, but little is known about a number of side effects. Here, we show that the cold receptor transient receptor potential melastatin 8 (TRPM8) undergoes a complex modulation by clinical concentrations of VAs in dorsal root ganglion neurons and HEK-293 cells heterologously expressing TRPM8. VAs produced a transient enhancement of TRPM8 through a depolarizing shift of its activation towards physiological membrane potentials, followed by a sustained TRPM8 inhibition. The stimulatory action of VAs engaged molecular determinants distinct from those used by the TRPM8 agonist. Transient TRPM8 activation by VAs could explain side effects such as inhibition of respiratory drive, shivering and the cooling sensation during the beginning of anaesthesia, whereas the second phase of VA action, that associated with sustained TRPM8 inhibition, might be responsible for hypothermia. Consistent with this, both hypothermia and the inhibition of respiratory drive induced by VAs are partially abolished in Trpm8-knockout animals. Thus, we propose TRPM8 as a new clinical target for diminishing common and serious complications of general anaesthesia.

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Section: Modulation By Vas Of Endogenous Trpm8 In Drg Neuronssupporting

confidence: 56%

Complex modulation of the cold receptor TRPM8 by volatile anaesthetics and its role in complications of general anaesthesia

Abeele

Kondratskyi

Dubois

et al. 2013

Journal of Cell Science

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“…It is activated by noxious cooling (< 17°C) (Story et al, 2003) and multiple pungent compounds including allyl isothiocyanate (Jordt et al, 2004;Bautista et al, 2005;Macpherson et al, 2005Macpherson et al, , 2007 and unsaturated aldehydes such as acrolein that are contained in cigarette smoke (Andrè et al, 2008(Andrè et al, , 2009Simon and Liedtke, 2008). Functional studies, channel localization, and analysis of TRPA1-deficient mice indicate that the channel is the primary molecular site through which they activate the pain pathway (Kwan et al, 2006;Levine and Alessandri-Haber, 2007).…”

Section: Introductionmentioning

confidence: 99%

Methylglyoxal activates the human transient receptor potential ankyrin 1 channel

et al. 2012

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-Methylglyoxal (MG) is an endogenous carbonyl compound that is produced in large quantity under hyperglycemic conditions, which are believed to contribute to the development of diabetic neuropathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear.In the present study, we investigated the effect of MG on transient receptor potential ankyrin 1 (TRPA1) activation in human TRPA1-expressing HEK293 cells. MG activated TRPA1-expressing HEK293 cells, but failed to activate human capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1)-expressing HEK293 cells or mock-transfected HEK293 cells. MG also induced calcium (Ca 2+ ) influx in a concentration-dependent manner, and the concentration-response curve indicates that the effect of MG has an EC 50 of 343.1 ± 17.3 μM. Interestingly, the time course in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in human TRPA1-expressing HEK293 showed considerable differences in response to MG and cinnamaldehyde. Furthermore, we examined four endogenous carbonyl compounds, including MG, glyceraldehyde, glycolaldehyde, and glyoxal; only MG notably activated TRPA1-expressing HEK293 cells. These results may provide insight into the TRPA1-mediated effects of MG on diabetic neuropathy.

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“…Recent studies have demonstrated an essential role of TRPA1 as a mediator of acute respiratory responses to the electrophilic and oxidizing chemicals acrolein and crotonaldehyde, which are common by-products of combustion (20,21); H 2 O 2 and HOCl (22), which activate TRPA1 through covalent modification of cysteine (C621, C641, and C665); and lysine (K710), referred to as the 3CK agonist site (23,24). Other nonelectrophilic compounds associated with DEP, including 3,5-ditert butylphenol (DTBP), activate TRPA1 through the menthol binding site (S873 T874; abbreviated as TRPA1-ST) (25).…”

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confidence: 99%

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

Deering-Rice

Shapiro

Romero

et al. 2015

Am J Respir Cell Mol Biol

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Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.

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How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways

Cited by 40 publications

References 26 publications

Complex modulation of the cold receptor TRPM8 by volatile anaesthetics and its role in complications of general anaesthesia

Complex modulation of the cold receptor TRPM8 by volatile anaesthetics and its role in complications of general anaesthesia

Methylglyoxal activates the human transient receptor potential ankyrin 1 channel

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

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