A-967079 / AbbVie 
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  • ||||||||||  A-967079 / AbbVie
    [VIRTUAL] TRPA1 BLOCK PROTECTS AGAINST LOSS OF WHITE MATTER FUNCTION DURING ISCHAEMIA IN THE MOUSE OPTIC NERVE (WSC 2021) -  Nov 7, 2021 - Abstract #519; Author: N. Hamilton-Whitaker;    
    TRPA1 block was effective when applied before, during or after OGD, indicating that TRPA1 mediated damage is occurring during ischaemia and during the recovery, but importantly that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain and that its block may be an effective therapeutic.
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    Journal:  The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma. (Pubmed Central) -  Oct 15, 2021   
    Furthermore, HO induced a TRPA1-dependent HO release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.
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    Journal:  Cannabidiol activation of vagal afferent neurons requires TRPA1. (Pubmed Central) -  Sep 23, 2020   
    Cannabis exposure reduced the magnitude of CBD responses likely due to a loss of TRPA1 signaling. Together these findings detail a novel excitatory action of CBD at vagal afferent neurons which requires TRPA1 and may contribute to the vagal mimetic effects of CBD and adaptation following chronic cannabis use.
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    Journal:  Gating and calcium-sensing mechanisms of TRPA1 channels revealed. (Pubmed Central) -  Aug 17, 2020   
    Novel structures of the human TRPA1 channel were determined in the presence of the agonist iodoacetamide and the antagonist A-967079, to reveal the open and closed states of the channel, respectively. The structures further revealed the location of Ca modulatory site that is likely conserved among several TRP subgroups.
  • ||||||||||  A-967079 / AbbVie
    Journal:  TRPV1 antagonist BCTC inhibits pH 6.0-induced pain in human skin. (Pubmed Central) -  Feb 29, 2020   
    A-967079 sensitizes pH responses is a TRPA1-responsive DRG neuron population, a direct effect of A-967079 on hTRPA1 and hTRPV1 was excluded. In conclusion, inhibiting TRPV1-mediated acidosis-induced pain could be a symptomatic and potentially also a disease-modifying approach.
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    Journal:  Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. (Pubmed Central) -  Feb 26, 2020   
    This effect was enhanced by pre-treatment with TNF suggesting that CBD preferentially targets activated, pro-inflammatory RASF. Thus, CBD possesses anti-arthritic activity and might ameliorate arthritis via targeting synovial fibroblasts under inflammatory conditions.
  • ||||||||||  A-967079 / AbbVie
    Journal; Preclinical:  Macrophages and Schwann cell TRPA1 mediate chronic allodynia in a mouse model of complex regional pain syndrome type I. (Pubmed Central) -  Nov 19, 2019   
    In the present mouse model of CRPS-I, we propose that the initial oxidative stress burst that follows reperfusion activates a feed forward mechanism that entails resident macrophages and Schwann cell TRPA1 of the injured tibial nerve to sustain chronic neuroinflammation and allodynia. Repeated treatment one hour before and for 3 days after I/R with a TRPA1 antagonist permanently protected CPIP mice against neuroinflammation and allodynia, indicating possible novel therapeutic strategies for CRPS-I.
  • ||||||||||  A-967079 / AbbVie
    TRPV1 antagonist BCTC inhibits pH 6.0-induced pain in human skin (Neuroscience 2019) -  Sep 2, 2019 - Abstract #055.02/I33; Author: S. HEBER, G. HARTNER, C. I. CIOTU, M. GOLD-BINDER, N. NINIDZE, A. GLEISS, H.-G. KRESS, M. J. FISCHER; Presentation Time: October 19, 2019; 14:00-15:00   
    The present study differs from the previous finding, which might be explained by the more relevant pH level. Inhibiting acidosis-induced pain could be a symptomatic and potentially also a disease-modifying approach.
  • ||||||||||  A-967079 / AbbVie
    The sensory irritant receptor TRPA1 is essential for airway inflammation in the LPS mouse model of acute lung injury. (ERS 2019) -  Aug 26, 2019 - Abstract #PA3885; Author: Ana Isabel Caceres; Sven-Eric Jordt; Presentation Time: October 01, 2019; 10:45-12:45   
    Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving the lung injury following inhaled LPS challenge. TRPA1 may represent a promising pharmacological target for the treatment of ALI, ARDS and other pulmonary inflammatory conditions.
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    TGFß1-induces resistance to apoptosis in human lung myofibroblasts via TRPA1 downregulation (ERS 2019) -  Aug 26, 2019 - Abstract #PA5378; Author: Harvinder Virk; Jamie Mccarthy; Emily Castells; Carol Feghali-Bostwick; Viona Bowman; Yassine Amrani; David Cousins; Peter Bradding; Katy Roach; Presentation Time: October 02, 2019; 10:45-12:45   
    Our data suggest that the downregulation of TRPA1 by TGFβ1 may protect HLMFs from apoptosis, promoting their persistence in IPF. Therapies that prevent this downregulation may have the potential to stop IPF progression.
  • ||||||||||  A-967079 / AbbVie
    Journal:  Effects of Cinnamaldehyde on Smooth Muscle Preparations. (Pubmed Central) -  Jun 3, 2019   
    It is suggested that CNA excites the muscles of the bladder via activation of capsaicin-sensitive nerves; in the ileum, it may interact with TRPA1 located on tissue elements that initiate both purinergic and cholinergic mechanisms. The relaxant effects of CNA may be due to the direct inhibition of the smooth muscles.
  • ||||||||||  A-967079 / AbbVie
    E-Liquid with Nicotine Causes Mucociliary Dysfunction Via TRPA1 Receptors in a Novel Large Animal Model of Exposure (ATS 2019) -  May 23, 2019 - Abstract #A4188/720; Author: N. Baumlin1; M. Kim1; S. Chung1; P. Whitney2; J. R. Sabater3; W. M. Abraham4; M. Salathe1;; Presentation Time: May 20, 2019; 14:15-16:15   
    EC vapor and fluid caused significant decreases in TMV and this reduction was dependent on TRPA1. This novel ovine exposure model is useful to examine the effects of EC vapor because: 1) sheep airways resemble human airways regarding MCC more closely than rodent airways; 2) exposures can be controlled and MCC measured in a non-anesthetized, awake animal; and 3) chronic exposures will be manageable.
  • ||||||||||  A-967079 / AbbVie
    The Role of TRPA1/TRPV1 in PM2.5 -Induced Airway Epithelial Cell Injury Model (ATS 2019) -  May 23, 2019 - Abstract #A7224/610; Author: F. Li, M. Wang;; Presentation Time: May 22, 2019; 13:30-15:30   
    Conclusion TRPA1/TRPV1 pathways are involved in the oxidative stress and inflammatory reaction of airway epithelial cells mediated by fine particulate matter (PM2.5). Inhibition of TRPA1/TPV1 pathway may be an intervention target for PM2.5 - mediated airway disease.
  • ||||||||||  A-967079 / AbbVie
    Journal:  Identification of possible hypoxia sensor for behavioral responses in a marine annelid, Capitella teleta. (Pubmed Central) -  Feb 13, 2019   
    Whole-mount in situ hybridization analysis showed that the gene was transcribed in the prostomium, where sensing functions are localized. These results suggested that the worm has a hypoxia-sensing system possibly utilizing CtTRPAbasal, and this system contributes to expanding the organism's niches in hypoxic environments by detecting whether hypoxia exceeds a level that would imperil its survival.
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    Journal:  ROS/TRPA1/CGRP signaling mediates cortical spreading depression. (Pubmed Central) -  Feb 6, 2019   
    ROS/TRPA1/CGRP signaling plays a critical role in regulating cortical susceptibility to CSD. Inhibition ROS and deactivation of TRPA1 channels may have therapeutic benefits in preventing stress-triggered migraine via CGRP.
  • ||||||||||  A-967079 / AbbVie
    Journal:  TRPV1 and TRPA1 in Lung Inflammation and Airway Hyperresponsiveness Induced by Fine Particulate Matter (PM). (Pubmed Central) -  Dec 7, 2018   
    Both TRPV1 and TRPA1 channels play an important role in PM-induced lung inflammation and AHR. However, inhibition of the TRPA1 channel or combined inhibition of TRPA1 and TRPV1 channels resulted in greater inhibitory effect on PM-induced lung injury through regulating the mitochondrial fission/fusion proteins and inhibiting the TLR4/NF-κB and NLRP3/caspase-1 pathways.
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    Journal:  CGRPergic Nerve TRPA1 Channels Contribute to Epigallocatechin Gallate-Induced Neurogenic Vasodilation. (Pubmed Central) -  Dec 5, 2018   
    Moreover, EGCG stimulated TRPA1-dependent intracellular Ca2+ elevation and CGRP release in a differentiated rat embryonic dorsal root ganglion/mouse neuroblastoma hybrid cell line. Together, these data suggest that EGCG-induced activation of TRPA1 channels in perivascular CGRPergic nerves decreases vascular resistance via Ca2+-dependent exocytosis of CGRP.
  • ||||||||||  A-967079 / AbbVie
    Journal:  A human TRPA1-specific pain model. (Pubmed Central) -  Dec 3, 2018   
    Further, the general possibility of quantitative inhibition of TRPA1 allows to identify the TRPA1-dependent disease component, given that the substance reaches its target. This contributes to a better understanding of pathophysiology, can lay the basis for new therapeutic approaches and can bridge the gap between preclinical research and clinical trials.
  • ||||||||||  A-967079 / AbbVie
    Journal:  Roles of TRPA1 and TRPV1 in Cigarette Smoke -induced Airway Epithelial Cell Injury Model. (Pubmed Central) -  Oct 1, 2018   
    They also prevented the changes in mitochondrial fission and fusion proteins and in MRC complexes activities induced by CSE. Both TRPA1 and TRPV1 mediate CSE-induced damage of airway and alveolar epithelial cells via modulation of oxidative stress, inflammation and mitochondrial damage and their inhibition should be considered as potential therapy for COPD.
  • ||||||||||  A-967079 / AbbVie
    Effects of exogenous cannabinoids on vagal afferent signaling (Neuroscience 2018) -  Sep 20, 2018 - Abstract #602.08 / HHH2; Author: *C. W. KOWALSKI1; F. J. SHAFFER2; J. E. M. LINDBERG2; B. PETERSON2; J. H. PETERS2; Presentation Time: November 06, 2018; 16:00-17:00   
    We investigated the effects of chronic cannabis vapor exposure on CBD and THC provoked calcium and current responses in dissociated nodose ganglia, on glutamate release in brainstem slices, and on expression of TRPA1, TRPV1, and CB1 in nodose ganglia and the NTS. Our findings demonstrate that CBD and THC effects on vagal neurotransmission are pleiotropic yet generally excitatory, putatively contributing to the autonomic effects of cannabis.
  • ||||||||||  A-967079 / AbbVie
    Journal; Preclinical:  Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain. (Pubmed Central) -  May 20, 2018   
    Whereas TRPV1, via an oxidative stress-independent pathway, contributes partially to heat hypersensitivity, oxidative stress-dependent activation of TRPA1 plays a key role in mediating thigmotaxis behavior and mechanical and cold allodynia in a cancer pain model. TRPA1 antagonists might be beneficial in the treatment of cancer pain.