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TRPA1 ion channel

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https://www.readbyqxmd.com/read/28399855/characterisation-of-a-murine-model-of-the-late-asthmatic-response
#1
Katie Baker, Kristof Raemdonck, Robert J Snelgrove, Maria G Belvisi, Mark A Birrell
BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the current available therapies are effective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In the search to understand disease pathogenesis and find effective therapies hypotheses are often tested in animal models before progressing into clinical studies. However, current dogma is that animal model data is often not predictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challenge induced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal model systems...
April 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#2
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28378773/polysulfides-h2sn-produced-from-the-interaction-of-hydrogen-sulfide-h2s-and-nitric-oxide-no-activate-trpa1-channels
#3
Ryo Miyamoto, Shin Koike, Yoko Takano, Norihiro Shibuya, Yuka Kimura, Kenjiro Hanaoka, Yasuteru Urano, Yuki Ogasawara, Hideo Kimura
Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca(2+) and H2Sn, showed that H2Sn and their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377424/the-ca2-permeable-cation-trpv3-channel-an-emerging-pivotal-target-for-itch-and-skin-diseases
#4
Gongxin Wang, Kewei Wang
Temperature-sensitive transient receptor potential (thermo-TRP) channels such as TRPA1 and TRPV1 have been indicated as downstream ion channel targets in transduction of itch. As a member of thermos-TRPs, Ca2+-permeable nonselective cation TRPV3 channels are expressed abundantly in the skin keratinocytes. Recent identification of gain-of-function mutations of human TRPV3 from patients with Olmsted Syndrome characterized by severe itching and palmoplantar and periorificial keratoderma unveils its crucial role in chronic itch and skin diseases...
April 4, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28332600/calmodulin-is-responsible-for-ca-2-dependent-regulation-of-trpa1-channels
#5
Raquibul Hasan, Alasdair T S Leeson-Payne, Jonathan H Jaggar, Xuming Zhang
TRPA1 is a Ca(2+)-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca(2+), with low Ca(2+) potentiating and high Ca(2+) inactivating TRPA1. However, it remains unknown how Ca(2+) exerts such contrasting effects. Here, we show that Ca(2+) regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca(2+)-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca(2+)-evoked potentiation of TRPA1 at low Ca(2+), but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca(2+)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#6
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28320952/identification-of-a-putative-binding-site-critical-for-general-anesthetic-activation-of-trpa1
#7
Hoai T Ton, Thieu X Phan, Ara M Abramyan, Lei Shi, Gerard P Ahern
General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABAA receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28293191/an-exploration-of-charge-compensating-ion-channels-across-the-phagocytic-vacuole-of-neutrophils
#8
Juliet R Foote, Philippe Behe, Mathew Frampton, Adam P Levine, Anthony W Segal
Neutrophils phagocytosing bacteria and fungi exhibit a burst of non-mitochondrial respiration that is required to kill and digest the engulfed microbes. This respiration is accomplished by the movement of electrons across the wall of the phagocytic vacuole by the neutrophil NADPH oxidase, NOX2. In this study, we have attempted to identify the non-proton ion channels or transporters involved in charge compensation by examining the effect of inhibitors on vacuolar pH and cross-sectional area, and on oxygen consumption...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28277613/activation-of-mutated-trpa1-ion-channel-by-resveratrol-in-human-prostate-cancer-associated-fibroblasts-caf
#9
Eric Vancauwenberghe, Lucile Noyer, Sandra Derouiche, Loïc Lemonnier, Pierre Gosset, Laura R Sadofsky, Pascal Mariot, Marine Warnier, Alexandre Bokhobza, Christian Slomianny, Brigitte Mauroy, Jean-Louis Bonnal, Etienne Dewailly, Philippe Delcourt, Laurent Allart, Natalia Prevarskaya, Morad Roudbaraki
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28239353/transient-receptor-potential-ankyrin-1-channel-expression-on-peripheral-blood-leukocytes-from-rheumatoid-arthritic-patients-and-correlation-with-pain-and-disability
#10
Ione Pereira, Saulo J F Mendes, Domingos M S Pereira, Thayanne F Muniz, Valderlane L P Colares, Cinara R A V Monteiro, Mahiba M R de S Martins, Marcos A G Grisotto, Valério Monteiro-Neto, Sílvio G Monteiro, João B Calixto, Susan D Brain, Elizabeth S Fernandes
Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA)...
2017: Frontiers in Pharmacology
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
#11
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...
March 22, 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
#12
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
#13
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
#14
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 affect 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 tumor growth...
March 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28076424/sensitization-of-trpa1-by-protein-kinase-a
#15
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
#16
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, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) to peripheral pain signaling. We first established a human pain model using intraepidermal injection of the 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
#17
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
#18
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
#19
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
#20
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
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