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TRPA1 ion channel

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https://www.readbyqxmd.com/read/29620434/transient-receptor-potential-polymorphism-and-haplotype-associate-with-crisis-pain-in-sickle-cell-disease
#1
Ellie H Jhun, Xiaoyu Hu, Nilanjana Sadhu, Yingwei Yao, Ying He, Diana J Wilkie, Robert E Molokie, Zaijie J Wang
AIM: Episodes of acute pain crisis contribute to considerable morbidity and mortality in sickle cell disease (SCD). Incomprehensive understanding of the underlying pain heterogeneity results in inadequate pain management. The transient receptor potential (TRP) family of voltage-gated ion channels acts as sensory transducers of diverse noxious stimuli. We performed an association study of polymorphisms in candidate genes TRPV1 and TRPA1 with pain in SCD patients. METHODS: Utilization rate, in other words, number of emergency department/acute care center admissions over 12 months as a result of pain crisis, served as a marker for acute pain...
April 5, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29603467/comparisons-of-behavioral-and-trpa1-heat-sensitivities-in-three-sympatric-cuban-anolis-lizards
#2
Hiroshi D Akashi, Shigeru Saito, Antonio Cádiz Díaz, Takashi Makino, Makoto Tominaga, Masakado Kawata
Thermal tolerances of organisms play a role in defining geographic ranges and occurrence of species. In Cuba, three sympatric species of Anolis lizards (Anolis allogus, Anolis homolechis, and Anolis sagrei) inhabit different thermal microhabitats. A previous study found that these species showed distinct gene expression patterns in response to temperature stimuli, suggesting the genetically distinct thermal physiology among species. To investigate whether the Anolis species inhabiting locally distinct thermal habitats diverge their thermal tolerances, we first conducted behavioral experiments to analyze the temperatures at which the three Anolis species escape from heat source...
March 30, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29596157/machine-learned-analysis-of-the-association-of-next-generation-sequencing-based-human-trpv1-and-trpa1-genotypes-with-the-sensitivity-to-heat-stimuli-and-topically-applied-capsaicin
#3
Dario Kringel, Gerd Geisslinger, Eduard Resch, Bruno G Oertel, Michael C Thrun, Sarah Heinemann, Jörn Lötsch
Heat pain and its modulation by capsaicin varies among subjects in experimental and clinical settings. A plausible cause is a genetic component, of which TRPV1 ion channels, by their response to both heat and capsaicin, are primary candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and carry genetic variants reported to modulate heat pain sensitivity. To address the role of these candidate genes in capsaicin induced hypersensitization to heat, pain thresholds acquired before and after topical application of capsaicin and TRPA1/TRPV1 exomic sequences derived by next-generation sequencing were assessed in n = 75 healthy volunteers and the genetic information comprised 278 loci...
March 27, 2018: Pain
https://www.readbyqxmd.com/read/29550417/trpa1-acts-in-a-protective-manner-in-imiquimod-induced-psoriasiform-dermatitis-in-mice
#4
Ágnes Kemény, Xenia Kodji, Szabina Horváth, Rita Komlódi, Éva Szőke, Zoltán Sándor, Anikó Perkecz, Csaba Gyömörei, György Sétáló, Balázs Kelemen, Tamás Bíró, Balázs István Tóth, Susan D Brain, Erika Pintér, Rolland Gyulai
The present study revealed the modulatory role of Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) cation channels in Aldara-induced (5% imiquimod, IMQ) murine psoriasis model using selective antagonists and genetically altered animals. We have also developed a refined localized model to enable internal controls and reduce systemic effects. Skin pathology was quantified by measuring skin thickness, scaling, blood flow and analyzing dermal cellular infiltrate, while nocifensive behaviours were also observed...
March 14, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29539642/a-trp-channel-trio-mediates-acute-noxious-heat-sensing
#5
Ine Vandewauw, Katrien De Clercq, Marie Mulier, Katharina Held, Silvia Pinto, Nele Van Ranst, Andrei Segal, Thierry Voet, Rudi Vennekens, Katharina Zimmermann, Joris Vriens, Thomas Voets
Acute pain represents a crucial alarm signal to protect us from injury. Whereas the nociceptive neurons that convey pain signals were described more than a century ago, the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified. Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional...
March 14, 2018: Nature
https://www.readbyqxmd.com/read/29535682/role-of-transient-receptor-potential-ankyrin-1-ion-channel-and-somatostatin-sst4-receptor-in-the-antinociceptive-and-anti-inflammatory-effects-of-sodium-polysulfide-and-dimethyl-trisulfide
#6
István Z Bátai, Ádám Horváth, Erika Pintér, Zsuzsanna Helyes, Gábor Pozsgai
Transient receptor potential ankyrin 1 (TRPA1) non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs) are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM) liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29497363/parathyroid-hormone-related-peptide-elicits-peripheral-trpv1-dependent-mechanical-hypersensitivity
#7
Andrew J Shepherd, Aaron D Mickle, Suraj Kadunganattil, Hongzhen Hu, Durga P Mohapatra
Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29420533/drosophila-gr64e-mediates-fatty-acid-sensing-via-the-phospholipase-c-pathway
#8
Hyeyon Kim, Haein Kim, Jae Young Kwon, Jeong Taeg Seo, Dong Min Shin, Seok Jun Moon
Animals use taste to sample and ingest essential nutrients for survival. Free fatty acids (FAs) are energy-rich nutrients that contribute to various cellular functions. Recent evidence suggests FAs are detected through the gustatory system to promote feeding. In Drosophila, phospholipase C (PLC) signaling in sweet-sensing cells is required for FA detection but other signaling molecules are unknown. Here, we show Gr64e is required for the behavioral and electrophysiological responses to FAs. GR64e and TRPA1 are interchangeable when they act downstream of PLC: TRPA1 can substitute for GR64e in FA but not glycerol sensing, and GR64e can substitute for TRPA1 in aristolochic acid but not N-methylmaleimide sensing...
February 8, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29363587/intracellular-cavity-of-sensor-domain-controls-allosteric-gating-of-trpa1-channel
#9
Lucie Zimova, Viktor Sinica, Anna Kadkova, Lenka Vyklicka, Vlastimil Zima, Ivan Barvik, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is a temperature-sensitive ion channel activated by various pungent and irritant compounds that can produce pain in humans. Its activation involves an allosteric mechanism whereby electrophilic agonists evoke interactions within cytosolic domains and open the channel pore through an integrated nexus formed by intracellular membrane proximal regions that are densely packed beneath the lower segment of the S1-S4 sensor domain. Studies indicate that this part of the channel may contain residues that form a water-accessible cavity that undergoes changes in solvation during channel gating...
January 23, 2018: Science Signaling
https://www.readbyqxmd.com/read/29352128/phosphorylation-of-the-transient-receptor-potential-ankyrin-1-by-cyclin-dependent-kinase-5-affects-chemo-nociception
#10
Bradford E Hall, Michaela Prochazkova, Matthew R Sapio, Paul Minetos, Natalya Kurochkina, B K Binukumar, Niranjana D Amin, Anita Terse, John Joseph, Stephen J Raithel, Andrew J Mannes, Harish C Pant, Man-Kyo Chung, Michael J Iadarola, Ashok B Kulkarni
Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and this interaction was blocked by TFP5, an inhibitor that prevents activation of Cdk5...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29336514/machine-learned-analysis-of-quantitative-sensory-testing-responses-to-noxious-cold-stimulation-in-healthy-subjects
#11
I Weyer-Menkhoff, M C Thrun, J Lötsch
BACKGROUND: Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. METHOD: Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers...
May 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29282613/regulation-of-pain-and-itch-by-trp-channels
#12
REVIEW
Carlene Moore, Rupali Gupta, Sven-Eric Jordt, Yong Chen, Wolfgang B Liedtke
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur...
February 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29274353/oxidative-stress-in-the-amygdala-contributes-to-neuropathic-pain
#13
B Sagalajev, H Wei, Z Chen, I Albayrak, A Koivisto, A Pertovaara
Earlier studies indicate that the central nucleus of the amygdala (CeA) contributes to neuropathic pain. Here we studied whether amygdaloid administration of antioxidants or antagonists of TRPA1 that is among ion channels activated by oxidative stress attenuates nociceptive or affective pain in experimental neuropathy, and whether this effect involves amygdaloid astrocytes or descending serotonergic pathways acting on the spinal 5-HT1A receptor. The experiments were performed in rats with spared nerve injury (SNI)...
December 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/29184198/activation-of-planarian-trpa1-by-reactive-oxygen-species-reveals-a-conserved-mechanism-for-animal-nociception
#14
Oscar M Arenas, Emanuela E Zaharieva, Alessia Para, Constanza Vásquez-Doorman, Christian P Petersen, Marco Gallio
All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is required for these responses. TRPA1-mutant Drosophila flies are also defective in noxious-heat responses. We find that either planarian or human TRPA1 can restore noxious-heat avoidance to TRPA1-mutant Drosophila, although neither is directly activated by heat...
December 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#15
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29129206/differential-cytotoxicity-and-intracellular-calcium-signalling-following-activation-of-the-calcium-permeable-ion-channels-trpv1-and-trpa1
#16
Thomas Stueber, Mirjam J Eberhardt, Yaki Caspi, Shaya Lev, Alexander Binshtok, Andreas Leffler
Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#17
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29038531/trpa1-fgfr2-binding-event-is-a-regulatory-oncogenic-driver-modulated-by-mirna-142-3p
#18
Jonathan Berrout, Eleni Kyriakopoulou, Lavanya Moparthi, Alexandra S Hogea, Liza Berrout, Cristina Ivan, Mihaela Lorger, John Boyle, Chris Peers, Stephen Muench, Jacobo Elies Gomez, Xin Hu, Carolyn Hurst, Thomas Hall, Sujanitha Umamaheswaran, Laura Wesley, Mihai Gagea, Michael Shires, Iain Manfield, Margaret A Knowles, Simon Davies, Klaus Suhling, Yurema Teijeiro Gonzalez, Neil Carragher, Kenneth Macleod, N Joan Abbott, George A Calin, Nikita Gamper, Peter M Zygmunt, Zahra Timsah
Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29034461/the-migraine-attack-as-a-homeostatic-neuroprotective-response-to-brain-oxidative-stress-preliminary-evidence-for-a-theory
#19
Jonathan M Borkum
BACKGROUND: Previous research has suggested that migraineurs show higher levels of oxidative stress (lipid peroxides) between migraine attacks and that migraine triggers may further increase brain oxidative stress. Oxidative stress is transduced into a neural signal by the TRPA1 ion channel on meningeal pain receptors, eliciting neurogenic inflammation, a key event in migraine. Thus, migraines may be a response to brain oxidative stress. RESULTS: In this article, a number of migraine components are considered: cortical spreading depression, platelet activation, plasma protein extravasation, endothelial nitric oxide synthesis, and the release of serotonin, substance P, calcitonin gene-related peptide, and brain-derived neurotrophic factor...
January 2018: Headache
https://www.readbyqxmd.com/read/28986540/reactive-metabolites-of-acetaminophen-activate-and-sensitize-the-capsaicin-receptor-trpv1
#20
Mirjam J Eberhardt, Florian Schillers, Esther M Eberhardt, Linus Risser, Jeanne de la Roche, Christine Herzog, Frank Echtermeyer, Andreas Leffler
The irritant receptor TRPA1 was suggested to mediate analgesic, antipyretic but also pro-inflammatory effects of the non-opioid analgesic acetaminophen, presumably due to channel activation by the reactive metabolites parabenzoquinone (pBQ) and N-acetyl-parabenzoquinonimine (NAPQI). Here we explored the effects of these metabolites on the capsaicin receptor TRPV1, another redox-sensitive ion channel expressed in sensory neurons. Both pBQ and NAPQI, but not acetaminophen irreversibly activated and sensitized recombinant human and rodent TRPV1 channels expressed in HEK 293 cells...
October 6, 2017: Scientific Reports
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