TRPA1: irritant detector of the airways

Gerhold, Kristin A.; Bautista, Diana M.

doi:10.1113/jphysiol.2008.158030

Cited by 24 publications

(12 citation statements)

References 8 publications

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“…Reactive chemicals such as AITC do not cause pain behavior in TRPA1 knockout mice, confirming that their actions are mediated exclusively by TRPA1 Kwan et al, 2006). These studies resulted in the proposal that TRPA1 acts as a sensor for reactive chemicals in the body (Gerhold and Bautista, 2008). In agreement with this hypothesis, it was reported that the endogenous aldehyde 4-hydroxynonenal (4-HNE) causes pain and neurogenic inflammation through activation of TRPA1 (Trevisani et al, 2007).…”

Section: Introductionsupporting

confidence: 67%

Mouse Monoclonal Antibodies to Transient Receptor Potential Ankyrin 1 Act as Antagonists of Multiple Modes of Channel Activation

Lee

Wang

Padaki

et al. 2014

J Pharmacol Exp Ther

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The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in different pathophysiologies that include asthma, cough, itch, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and pain behaviors in rodents. Hence, TRPA1 antagonists are being pursued as potential therapeutics. With the goal of generating monoclonal antibodies (mAbs) to human TRPA1 that could act as selective antagonists, we immunized mice with a variety of antigens expressing TRPA1 channels. After generation of hybridomas, the hybridoma conditioned media were screened to identify the mAbs that bind TRPA1 channels by a flow cytometry assay utilizing U2OS or Chinese hamster ovary (CHO) cells stably expressing TRPA1. The purified IgGs from the hybridomas that showed selective binding to TRPA1 were evaluated for antagonism in agonist-induced 45 Ca 21 uptake assays using CHO-TRPA1 cells. Several of the mAbs showed concentration-dependent inhibition of AITC and cold (4°C) activation of TRPA1. The most potent mAb, 2B10, had IC 50 values of approximately 260 and 90 nM in the two assays, respectively. These antagonist mAbs also blocked osmotically activated TRPA1 as well as activation by an endogenous agonist (4-oxo-2-nonenal). In summary, we generated mouse mAbs against TRPA1 that act as antagonists of multiple modes of TRPA1 activation.

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Section: Introductionsupporting

confidence: 67%

Mouse Monoclonal Antibodies to Transient Receptor Potential Ankyrin 1 Act as Antagonists of Multiple Modes of Channel Activation

Lee

Wang

Padaki

et al. 2014

J Pharmacol Exp Ther

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“…). One of the most commonly expressed subtypes of TRP channels in the airways is the TRP ankyrin (A) 1 channel, which has emerged as a major irritant detector . It has been shown that TRPA1 is activated in vitro by irritants such as acrolein, tear gas, vehicle exhaust , ozone , hydrogen peroxide, and hypochlorite .…”

Section: Pathophysiological Mechanisms Involved In Occupational Airwamentioning

confidence: 99%

Occupational upper airway disease: how work affects the nose

Hox

Steelant

Fokkens

et al. 2014

Allergy

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Chronic inflammation of the upper airways is common and can arbitrarily be divided into rhinitis and rhinosinusitis. Infection and allergy represent two wellcharacterized and most frequently diagnosed etiologies of upper airway inflammation. Persistent upper airway inflammation caused by agents inhaled in the work environment represents a diagnostic challenge in clinical practice, and its pathophysiology has been little studied. Occupational rhinitis is a recognized medical condition with diagnostic and therapeutic guidelines. In contrast, only limited evidence is available about the relationship between work exposures and rhinosinusitis. This review aims at providing a comprehensive overview of the available literature on occupational upper airway disease with a focus on pathophysiological mechanisms and with an emphasis on the current unmet needs in work-related upper airway disease.

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“…Nasal nociceptive stimulation was performed by TRPA1 agonists allyl-isothiocyanate (AITC) and cinnamaldehyde which actually may represent a model for air-born irritants induced signalling [10] . The broad spectrum of irritants like acrolein, isocyanates, oxidizing substances and other pollutants activate the cation channel TRPA1 by covalent modification of the channel protein [11,12]. Activation of this channel leads to a sensation of airway irritation [13].…”

Section: Introductionmentioning

confidence: 99%

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels

Buday

Brozmanová

Biringerová

et al. 2012

Cough

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BackgroundCough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. In animal models, modulation of cough by nasal afferent inputs can either facilitate or inhibit the cough response, depending on the type of trigeminal afferents stimulated.MethodsIn this study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with isocyanate (AITC), cinnamaldehyde, (−) menthol and (+) menthol (all 10-3 M) nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response were measured).ResultsNasal challenges with TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p<0.05) but no statistically significant modulation of the C2 and cumulative cough response. In contrast, both TRPM8 agonists administered to the nose significantly modulated all parameters including C2 (p<0.05), Cu (p<0.01) and cumulative cough response (p <0.01) documenting strong anti irritating potential of menthol isomers.ConclusionsIn addition to trigeminal afferents expressing TRP channels, olfactory nerve endings, trigemino – olfactoric relationships, the smell perception process and other supramedullar influences should be considered as potential modulators of the cough response in humans.

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TRPA1: irritant detector of the airways

Cited by 24 publications

References 8 publications

Mouse Monoclonal Antibodies to Transient Receptor Potential Ankyrin 1 Act as Antagonists of Multiple Modes of Channel Activation

Mouse Monoclonal Antibodies to Transient Receptor Potential Ankyrin 1 Act as Antagonists of Multiple Modes of Channel Activation

Occupational upper airway disease: how work affects the nose

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels

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