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TRPA1 ion channel

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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
#1
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 as they responded to the electrophilic compounds allyl isothiocyanate (AITC) and cinnamaldehyde as well as heat...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27835802/transient-receptor-potential-channels-in-neuropathic-pain
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
October 18, 2016: Inflammopharmacology
https://www.readbyqxmd.com/read/27738742/n-acetyl-l-cysteine-inhibits-sulfur-mustard-induced-and-trpa1-dependent-calcium-influx
#12
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
https://www.readbyqxmd.com/read/27735854/effects-of-food-components-that-activate-trpa1-receptors-on-mucosal-ion-transport-in-the-mouse-intestine
#13
Linda J Fothergill, Brid Callaghan, Leni R Rivera, TinaMarie Lieu, Daniel P Poole, Hyun-Jung Cho, David M Bravo, John B Furness
TRPA1 is a ligand-activated cation channel found in the intestine and other tissues. Components of food that stimulate TRPA1 receptors (phytonutrients) include allyl isothiocyanate, cinnamaldehyde and linalool, but these may also act at other receptors. Cells lining the intestinal mucosa are immunoreactive for TRPA1 and Trpa1 mRNA occurs in mucosal extracts, suggesting that the TRPA1 receptor is the target for these agonists. However, in situ hybridisation reveals Trpa1 expression in 5-HT containing enteroendocrine cells, not enterocytes...
October 10, 2016: Nutrients
https://www.readbyqxmd.com/read/27734949/trpv1-dysfunction-in-cystinosis-patients-harboring-the-homozygous-57%C3%A2-kb-deletion
#14
L Buntinx, T Voets, B Morlion, L Vangeel, M Janssen, E Cornelissen, J Vriens, J de Hoon, E Levtchenko
Cystinosis is a rare autosomal recessive disorder characterized by lysosomal cystine accumulation due to loss of function of the lysosomal cystine transporter (CTNS). The most common mutation in cystinosis patients of Northern Europe consists of a 57-kb deletion. This deletion not only inactivates the CTNS gene but also extends into the non-coding region upstream of the start codon of the TRPV1 gene, encoding the capsaicin- and heat-sensitive ion channel TRPV1. To evaluate the consequences of the 57-kb deletion on functional TRPV1 expression, we compared thermal, mechanical and chemical sensitivity of cystinosis patients with matched healthy controls...
October 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27718297/trpa1-receptor-is-upregulated-in-human-oral-lichen-planus
#15
J Kun, A Perkecz, L Knie, G Sétáló, T Tornóczki, E Pintér, Á Bán
OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with antigen-specific and non-specific mechanisms. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel activated by noxious stimuli such as oxidative stress products evoking pain and release of proinflammatory mediators from sensory nerve endings culminating in neurogenic inflammation. Extraneuronal TRPA1s, for example, on immune cells possess yet unknown functions. SUBJECTS AND METHODS: We studied the buccal mRNA expression (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors and key OLP mediator transcripts in oral mucosa samples of healthy volunteers (n = 9), OLP patients (n = 43), and OLP-like hyperkeratotic patients (n = 12)...
October 8, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27687800/participation-of-peripheral-trpv1-trpv4-trpa1-and-asic-in-a-magnesium-sulfate-induced-local-pain-model-in-rat
#16
Dragana Srebro, Sonja Vučković, Milica Prostran
We previously showed that magnesium sulfate (MS) has systemic antinociceptive and local peripheral pronociceptive effects. The role of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action of MS has not been investigated in detail. The aim of this study was to explore the participation of TRP channels in the pronociceptive action of MS in rats after its intraplantar injection. The paw withdrawal threshold (PWT) to mechanical stimuli was measured by the electronic von Frey test...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27589700/cardamonin-a-novel-antagonist-of-htrpa1-cation-channel-reveals-therapeutic-mechanism-of-pathological-pain
#17
Shifeng Wang, Chenxi Zhai, Yanling Zhang, Yangyang Yu, Yuxin Zhang, Lianghui Ma, Shiyou Li, Yanjiang Qiao
The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27582506/effects-of-n-glycosylation-of-the-human-cation-channel-trpa1-on-agonist-sensitivity
#18
Timothy James Egan, Mario A Acuña, Marcy Zenobi-Wong, Hanns Ulrich Zeilhofer, David Urech
Determining the functional significance of post-translational modifications advances our understanding of many broadly-expressed proteins, and particularly ion channels. The enzymes that catalyze these modifications are often expressed in a cell-type specific manner, resulting in considerable structural diversity among post-translationally modified proteins that are expressed across a variety of cell types. TRP channels exhibit notably variable behavior between cell types in vitro and in vivo , and they are frequently modified with N-glycans that contribute to protein function...
August 31, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27555550/rat-odontoblasts-may-use-glutamate-to-signal-dentin-injury
#19
Yi Sul Cho, Chang Hyun Ryu, Jong Hwa Won, Hue Vang, Seog Bae Oh, Jin Young Ro, Yong Chul Bae
Accumulating evidence indicates that odontoblasts act as sensor cells, capable of triggering action potentials in adjacent pulpal nociceptive axons, suggesting a paracrine signaling via a currently unknown mediator. Since glutamate can mediate signaling by non-neuronal cells, and peripheral axons may express glutamate receptors (GluR), we hypothesized that the expression of high levels of glutamate, and of sensory receptors in odontoblasts, combined with an expression of GluR in adjacent pulpal axons, is the morphological basis for odontoblastic sensory signaling...
October 29, 2016: Neuroscience
https://www.readbyqxmd.com/read/27545873/alternative-in-vitro-assays-to-assess-the-potency-of-sensory-irritants-is-one-trp-channel-enough
#20
Ramona Lehmann, Hanns Hatt, Christoph van Thriel
One important function of the peripheral nervous system is the detection of noxious chemicals in the environment as well as the recognition of tissue damage throughout the body. Transient receptor potential (TRP) ion channels are able to sense a multitude of signaling factors involved in these processes. Via the sensory ganglia these sentinels convey information to the central nervous system, where perceptions of nociception or sensory irritation are generated. From the 28 members of the 6 subfamilies present in mammals, researchers in toxicology paid special attention to TRPA1 and TRPV1 channels...
August 18, 2016: Neurotoxicology
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