The role of TRPA1 in visceral inflammation and pain

Lapointe, Tamia K.; Altier, Christophe

doi:10.4161/chan.5.6.18016

Cited by 58 publications

(44 citation statements)

References 60 publications

(86 reference statements)

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“…Inhibition of TRPA1 by a potent and selective antagonist [A-967079; (1E,3E)-1-(4-fluorophenyl)-2-methyl-1-pentene-3-one oxime] relieved cold allodynia in a chronic constriction injury model of pain and reversed the grip force deficit in an monoiodoacetateinduced osteoarthritis model (Chen et al, 2011). In all, these studies suggest that TRPA1 is a potential target for novel therapeutics (McMahon and Wood, 2006;Viana and FerrerMontiel, 2009;Lapointe and Altier, 2011;Strassmaier and Bakthavatchalam, 2011;Meseguer et al, 2014). Based on the published feasibility (Xu et al, 2005;Klionsky et al, 2006;Gómez-Varela et al, 2007;Naylor and Beech, 2009;Sun and Li, 2013), we attempted to generate monoclonal antagonist antibodies to TRPA1.…”

Section: Introductionmentioning

confidence: 89%

“…Trevisani et al (2007) previously reported that excess accumulation of reactive oxygen species produced at inflammatory sites leads to the production of reactive chemicals, such as 4-ONE, a product of lipid peroxidation. Previous reports indicate that these products of lipid peroxidation activate TRPA1 and may contribute to inflammatory pain behavior in rodent models of inflammation (McMahon and Wood, 2006;McGaraughty et al, 2010;Lapointe and Altier, 2011). To evaluate the ability of the antagonist mAbs to block TRPA1 activation by reactive lipid peroxidation products, we first determined the EC 90 values for 4-ONE, 4-HNE, and 4-hydroxyhexenal in their concentration-dependent curves of 45 Ca 21 uptake into CHO-TRPA1 cells.…”

Section: Camentioning

confidence: 99%

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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: Introductionmentioning

confidence: 89%

Section: Camentioning

confidence: 99%

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

View full text Add to dashboard Cite

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“…The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain due to their ability to be activated by nociceptive signals and sensitized by proinflammatory mediators, including in the context of visceral inflammation and pain in the GI and urinary tracts [85]. Apart from TRPV1, the pharmacology of this channel family is still insufficiently known [86].…”

Section: Painmentioning

confidence: 99%

The prolactin receptor as a therapeutic target in human diseases: browsing new potential indications

Goffin

Touraine

2015

Expert Opinion on Therapeutic Targets

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“…These fi ndings suggest that TLR7 interacts directly with TRPA1 in nociceptive neurons to mediate let-7b-induced pain signaling. Classically, TRPA1 activation by infl ammatory and noxious stimuli depends on heterotrimeric G proteins, protein kinase A, protein kinase C, and phospholipase C (11). However, none of these signaling molecules were necessary for let-7b-induced activation (9).…”

mentioning

confidence: 97%

Location Is Everything: let-7b microRNA and TLR7 Signaling Results in a Painful TRP

2014

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Extracellular let-7b, a microRNA found in the central nervous system, affects neurons through its interaction with Toll-like receptor 7 (TLR7), but with divergent outcomes in different neurons. Lehmann et al. found that let-7b stimulation of cortical and hippocampal neurons led to neuronal apoptosis, whereas Park et al. report that let-7b activation of TLR7 stimulated the cation channel transient receptor potential A1 (TRPA1) on dorsal root ganglia sensory neurons and induced pain responses. The primary difference that may influence these distinct responses to let-7b is the localization of TLR7 to the endosome in the cortical and hippocampal neurons or the plasma membrane in the sensory neurons. These studies suggest that different types of neurons traffic TLR7 to distinct membrane locations, affecting the functional response of neurons to let-7b stimulation.

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The role of TRPA1 in visceral inflammation and pain

Cited by 58 publications

References 60 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

The prolactin receptor as a therapeutic target in human diseases: browsing new potential indications

Location Is Everything: let-7b microRNA and TLR7 Signaling Results in a Painful TRP

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