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TRPA1 ion channel

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https://www.readbyqxmd.com/read/28213106/oral-treatment-with-essential-oil-of-hyptis-spicigera-lam-lamiaceae-reduces-acute-pain-and-inflammation-in-mice-potential-interactions-with-transient-receptor-potential-trp-ion-channels
#1
Róli Rodrigues Simões, Igor Dos Santos Coelho, Stella Célio Junqueira, Glauce Regina Pigatto, Marcos José Salvador, Adair Roberto Soares Santos, Felipe Meira de Faria
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. AIM OF THE STUDY: The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. MATERIAL AND METHODS: The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28197074/the-first-extracellular-linker-is-important-for-several-aspects-of-the-gating-mechanism-of-human-trpa1-channel
#2
Lenka Marsakova, Ivan Barvik, Vlastimil Zima, Lucie Zimova, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28187208/respiratory-virus-infection-up-regulates-trpv1-trpa1-and-asics3-receptors-on-airway-cells
#3
Shadia Omar, Rebecca Clarke, Haniah Abdullah, Clare Brady, John Corry, Hanagh Winter, Olivier Touzelet, Ultan F Power, Fionnuala Lundy, Lorcan P A McGarvey, S Louise Cosby
Receptors implicated in cough hypersensitivity are transient receptor potential vanilloid 1 (TRPV1), transient receptor potential cation channel, Subfamily A, Member 1 (TRPA1) and acid sensing ion channel receptor 3 (ASIC3). Respiratory viruses, such as respiratory syncytial virus (RSV) and measles virus (MV) may interact directly and/or indirectly with these receptors on sensory nerves and epithelial cells in the airways. We used in vitro models of sensory neurones (SHSY5Y or differentiated IMR-32 cells) and human bronchial epithelium (BEAS-2B cells) as well as primary human bronchial epithelial cells (PBEC) to study the effect of MV and RSV infection on receptor expression...
2017: PloS One
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#4
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely impact human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of Vascular Endothelial Growth Factor (VEGF), a factor known to promote tumour growth...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28076424/sensitization-of-trpa1-by-protein-kinase-a
#5
Jannis E Meents, Michael J M Fischer, Peter A McNaughton
The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1...
2017: PloS One
https://www.readbyqxmd.com/read/28062311/trpa1-and-trpv1-antagonists-do-not-inhibit-human-acidosis-induced-pain
#6
Matthias G Schwarz, Barbara Namer, Peter W Reeh, Michael J M Fischer
: Acidosis occurs in a variety of pathophysiological and painful conditions where it is thought to excite or contribute to excitation of nociceptive neurons. Despite potential clinical relevance the principal receptor for sensing acidosis is unclear, but several receptors have been proposed. We investigated the contribution of the acid sensing ion channels, TRPV1 and TRPA1 to peripheral pain signaling. We first established a human pain model using intra-epidermal injection of TRPA1 agonist carvacrol...
January 3, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28043013/transient-receptor-potential-melastatin-trpm-8-is-expressed-in-freshly-isolated-native-human-odontoblasts
#7
Kento Tazawa, Hideharu Ikeda, Nobuyuki Kawashima, Takashi Okiji
OBJECTIVE: Cold-sensitive ion channels, such as transient receptor potential melastatin (TRPM) 8 and transient receptor potential ankyrin (TRPA) 1, may play a crucial role in the nociceptive function of odontoblasts, whereas expression of these TRP channels in human native odontoblasts remains to be elucidated. This study aimed to analyze the expression of TRPM8 and TRPA1 in freshly isolated native human odontoblasts. DESIGN: Odontoblasts were isolated from freshly extracted healthy human teeth (n=4); after removing the inner pulp tissues from the pulp chambers, odontoblasts remaining on the dentin surface were washed out with phosphate buffered saline and collected...
December 23, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27978803/magnesium-in-pain-research-state-of-the-art
#8
Dragana Srebro, Sonja Vučković, Aleksandar Milovanović, Jovan Košutić, Katarina Savić Vujović, Milica Prostran
Magnesium has been shown to produce an antinociceptive effect on animal models of neuropathic and inflammatory pain. It has also been shown to exert an analgesic effect on humans in conditions presenting acute (postoperative pain) and chronic (neuropathic) pain. As it is known that magnesium is a physiological antagonist of the N-methyl-D-aspartate (NMDA) receptor ion channel, and that the NMDA receptor plays a key role in central sensitization, the primary mechanism through which magnesium produces its analgesic effect is believed to be blockade of the NMDA receptor in the spinal cord...
December 12, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27875296/the-n-terminal-ankyrin-repeat-domain-is-not-required-for-electrophile-and-heat-activation-of-the-purified-mosquito-trpa1-receptor
#9
Sabeen Survery, Lavanya Moparthi, Per Kjellbom, Edward D Högestätt, Peter M Zygmunt, Urban Johanson
Temperature sensors are crucial for animals to optimize living conditions. The temperature response of the ion channel transient receptor potential A1 (TRPA1) is intriguing; some orthologs have been reported to be activated by cold and others by heat, but the molecular mechanisms responsible for its activation remain elusive. Single-channel electrophysiological recordings of heterologously expressed and purified Anopheles gambiae TRPA1 (AgTRPA1), with and without the N-terminal ankyrin repeat domain, demonstrate that both proteins are functional because they responded to the electrophilic compounds allyl isothiocyanate and cinnamaldehyde as well as heat...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27835802/transient-receptor-potential-channels-in-neuropathic-pain
#10
REVIEW
Lilian Basso, Christophe Altier
Neuropathic pain caused by disease or dysfunction of the nervous system is one of the most difficult pain conditions to treat. Symptoms include a hypersensitivity to mechanical and thermal stimuli, processed by specialized nociceptors that constitute the first line of defence of the somatosensory system. The detection of these stimuli depends on the TRP ion channel family, which activates upon damaging pressure, extreme temperature, or toxic endogenous and exogenous chemicals. This review will summarize the current knowledge of the contribution of TRP channels, particularly the thermosensitive TRP, including TRPV1, TRPA1 and TRPM8 channels that play a central role in the sensitization of nociceptive transduction...
October 27, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27832523/ovariectomy-induced-mitochondrial-oxidative-stress-apoptosis-and-calcium-ion-influx-through-trpa1-trpm2-and-trpv1-are-prevented-by-17%C3%AE-estradiol-tamoxifen-and-raloxifene-in-the-hippocampus-and-dorsal-root-ganglion-of-rats
#11
Yener Yazğan, Mustafa Nazıroğlu
Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca(2+) influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca(2+) influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats...
November 10, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27827953/blocking-trpa1-in-respiratory-disorders-does-it-hold-a-promise
#12
REVIEW
Indranil Mukhopadhyay, Abhay Kulkarni, Neelima Khairatkar-Joshi
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of "chemosensor", detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis...
November 5, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27827430/lactate-is-a-potent-inhibitor-of-the-capsaicin-receptor-trpv1
#13
Jeanne de la Roche, Isabella Walther, Waleria Leonow, Axel Hage, Mirjam Eberhardt, Martin Fischer, Peter W Reeh, Susanne Sauer, Andreas Leffler
Tissue ischemia results in an accumulation of lactate and local or systemic lactic acidosis. In nociceptive sensory neurons, lactate was reported to sensitize or activate the transient receptor potential ion channel TRPA1 and acid-sensing ion channels (ASICs). However, it is unclear how lactate modulates the TRPV1 regarded as the main sensor for acidosis in sensory neurons. In this study we investigated the effects of lactate (LA) on recombinant and native TRPV1 channels and on TRPV1-mediated release of neuropeptides from mouse nerves...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27824920/the-outer-pore-and-selectivity-filter-of-trpa1
#14
Adam P Christensen, Nurunisa Akyuz, David P Corey
TRPA1 (transient-receptor-potential-related ion channel with ankyrin domains) is a direct receptor or indirect effector for a wide variety of nociceptive signals, and thus is a compelling target for development of analgesic pharmaceuticals such as channel blockers. Recently, the structure of TRPA1 was reported, providing insights into channel assembly and pore architecture. Here we report whole-cell and single-channel current recordings of wild-type human TRPA1 as well as TRPA1 bearing point mutations of key charged residues in the outer pore...
2016: PloS One
https://www.readbyqxmd.com/read/27823962/the-transient-receptor-potential-ankyrin-1-mediates-mechanical-hyperalgesia-induced-by-the-activation-of-b1-receptor-in-mice
#15
Flavia Carla Meotti, Cláudia Pinto Figueiredo, Marianne Manjavachi, João B Calixto
The kinin receptor B1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B1 receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B1 agonist des-Arginine(9)-bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw...
November 4, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27812120/oxidized-phospholipid-oxpapc-activates-trpa1-and-contributes-to-chronic-inflammatory-pain-in-mice
#16
Boyi Liu, Yan Tai, Ana I Caceres, Satyanarayana Achanta, Shrilatha Balakrishna, Xiaomei Shao, Junfan Fang, Sven-Eric Jordt
Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8...
2016: PloS One
https://www.readbyqxmd.com/read/27799365/a-painful-tr-i-p-to-lysosomes
#17
Mingxue Gu, Haoxing Xu
The ion channel TRPA1 detects noxious stimuli at the plasma membrane of neurons and elicits pain and inflammation. In this issue, Shang et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603081) report that TRPA1 also localizes to lysosomal membranes of neurons, releasing intracellular Ca(2+) to trigger vesicle exocytosis and neuropeptide release.
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27779810/trpa1-gene-polymorphisms-and-childhood-asthma
#18
Valentina Gallo, F Nicole Dijk, John W Holloway, Susan M Ring, Gerard H Koppelman, Dirkje S Postma, David P Strachan, Raquel Granell, Johan C de Jongste, Vincent W V Jaddoe, Herman T den Dekker, Liesbeth Duijts, A John Henderson, Seif O Shaheen
BACKGROUND: Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. METHODS: We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7...
October 25, 2016: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/27757589/trp-channels-potential-drug-target-for-neuropathic-pain
#19
REVIEW
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Ranjana Bhandari, Anurag Kuhad
Neuropathic pain is a debilitating disease which affects central as well as peripheral nervous system. Transient receptor potential (TRP) channels are ligand-gated ion channels that detect physical and chemical stimuli and promote painful sensations via nociceptor activation. TRP channels have physiological role in the mechanisms controlling several physiological responses like temperature and mechanical sensations, response to painful stimuli, taste, and pheromones. TRP channel family involves six different TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1) which are expressed in pain sensing neurons and primary afferent nociceptors...
December 2016: Inflammopharmacology
https://www.readbyqxmd.com/read/27738742/n-acetyl-l-cysteine-inhibits-sulfur-mustard-induced-and-trpa1-dependent-calcium-influx
#20
Bernhard Stenger, Tanja Popp, Harald John, Markus Siegert, Amelie Tsoutsoulopoulos, Annette Schmidt, Harald Mückter, Thomas Gudermann, Horst Thiermann, Dirk Steinritz
Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target...
October 13, 2016: Archives of Toxicology
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