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TRPA1 ion channel

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
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
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
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
József Kun, Anikó Perkecz, Lorenz Knie, György Sétáló, Tamás Tornóczki, Erika Pintér, Ágnes 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 e.g. on immune cells possess yet unkown 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 diseases (n=12)...
October 8, 2016: Oral Diseases
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...
September 28, 2016: Neuroscience
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
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
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
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
Chun-Hsiang Tan, Peter A McNaughton
Thermally activated ion channels are known to detect the entire thermal range from extreme heat (TRPV2), painful heat (TRPV1, TRPM3 and ANO1), non-painful warmth (TRPV3 and TRPV4) and non-painful coolness (TRPM8) through to painful cold (TRPA1). Genetic deletion of each of these ion channels, however, has only modest effects on thermal behaviour in mice, with the exception of TRPM8, the deletion of which has marked effects on the perception of moderate coolness in the range 10-25 °C. The molecular mechanism responsible for detecting non-painful warmth, in particular, is unresolved...
August 25, 2016: Nature
M Levanti, B Randazzo, E Viña, G Montalbano, O Garcia-Suarez, A Germanà, J A Vega, F Abbate
Sensory information from the environment is required for life and survival, and it is detected by specialized cells which together make up the sensory system. The fish sensory system includes specialized organs that are able to detect mechanical and chemical stimuli. In particular, taste buds are small organs located on the tongue in terrestrial vertebrates that function in the perception of taste. In fish, taste buds occur on the lips, the flanks, and the caudal (tail) fins of some species and on the barbels of others...
September 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Meng-Qi Yang, Lin-Lan Ye, Xiao-Ling Liu, Xiao-Ming Qi, Jia-Di Lv, Gang Wang, Ulah-Khan Farhan, Nawaz Waqas, Ding-Ding Chen, Lei Han, Xiao-Hui Zhou
TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies...
June 2016: Chinese Journal of Natural Medicines
Florian Schillers, Esther Eberhardt, Andreas Leffler, Mirjam Eberhardt
Propacetamol (PPCM) is a prodrug of paracetamol (PCM), which was generated to increase water solubility of PCM for intravenous delivery. PPCM is rapidly hydrolyzed by plasma esterases to PCM and diethylglycine and shares some structural and metabolic properties with lidocaine. Although PPCM is considered to be comparable to PCM regarding its analgesic properties, injection pain is a common side effect described for PPCM but not PCM. Injection pain is a frequent and unpleasant side effect of numerous drugs in clinical use, and previous reports have indicated that the ligand gated ion channels transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) can mediate this effect on sensory neurons...
October 2016: Journal of Pharmacology and Experimental Therapeutics
Elisangela Bressan, Filip Touska, Irina Vetter, Katrin Kistner, Tatjana I Kichko, Nathália B Teixeira, Gisele Picolo, Yara Cury, Richard J Lewis, Michael J M Fischer, Katharina Zimmermann, Peter W Reeh
Crotalphine is a structural analogue to a novel analgesic peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. Although crotalphine's analgesic effect is well established, its direct mechanism of action remains unresolved. The aim of the present study was to investigate the effect of crotalphine on ion channels in peripheral pain pathways. We found that picomolar concentrations of crotalphine selectively activate heterologously expressed and native TRPA1 ion channels...
November 2016: Pain
Craig Rothenberg, Satyanarayana Achanta, Erik R Svendsen, Sven-Eric Jordt
Deployments of tear gas and pepper spray have rapidly increased worldwide. Large amounts of tear gas have been used in densely populated cities, including Cairo, Istanbul, Rio de Janeiro, Manama (Bahrain), and Hong Kong. In the United States, tear gas was used extensively during recent riots in Ferguson, Missouri. Whereas tear gas deployment systems have rapidly improved-with aerial drone systems tested and requested by law enforcement-epidemiological and mechanistic research have lagged behind and have received little attention...
July 8, 2016: Annals of the New York Academy of Sciences
Melissa Gómez, Alberto González, Claudio A Sáez, Alejandra Moenne
The marine macroalga Ulva compressa (Chlorophyceae) is a cosmopolitan species, tolerant to heavy metals, in particular to copper. U. compressa was cultivated with 10 μM copper for 12 h and membrane depolarization events were detected. First, seven depolarization events occurred at 4, 8, 12-13, 80, and 86 min, and at 5 and 9 h of copper exposure. Second, bathocuproine sulphonate, a specific copper-chelating compound, was added before incorporating copper to the culture medium. Copper-induced depolarizations were inhibited by bathocuproine at 4, 8, 12-13, 80, and 86 min, but not at 5 and 9 h, indicating that initial events are due to copper ions entry...
2016: Frontiers in Plant Science
Anna D Holmes, Martin Steinhoff
Rosacea is a chronic relapsing inflammatory skin disease with high prevalence world-wide. Recent research suggests that dysregulation of innate and adaptive immune pathways as well as neuro-vascular changes are present, with different degrees of importance in the various subtypes. Neither the etiology, genetics, nor pathophysiological basis of the vascular, inflammatory or fibrotic changes are well understood. The clinical spectrum comprises a huge variability from erythema (vasodilation) to papules/pustules (inflammatory infiltrate) to phymata (fibrosis, glandular hyperplasia) making it a valuable human disease model to understand the interplay between the neurovascular and immune systems as well as the progression from chronic inflammation to fibrosis in skin...
July 4, 2016: Experimental Dermatology
Paraskevi Sakellariou, Angelica Valente, Andres E Carrillo, George S Metsios, Liliya Nadolnik, Athanasios Z Jamurtas, Yiannis Koutedakis, Cesar Boguszewski, Cláudia Marlise Balbinotti Andrade, Per-Arne Svensson, Nair Honda Kawashita, Andreas D Flouris
INTRODUCTION: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT...
August 2016: Medical Hypotheses
Luca Avenali, Oli Abate Fulas, Julia Sondermann, Pratibha Narayanan, David Gomez-Varela, Manuela Schmidt
The ability of sensory neurons to detect potentially harmful stimuli relies on specialized molecular signal detectors such as transient receptor potential (TRP) A1 ion channels. TRPA1 is critically implicated in vertebrate nociception and different pain states. Furthermore, TRPA1 channels are subject to extensive modulation and regulation - processes which consequently affect nociceptive signaling. Here we show, that the neuropeptide Nocistatin sensitizes TRPA1-dependent calcium influx upon application of the TRPA1 agonist mustard oil (MO) in cultured sensory neurons of dorsal root ganglia (DRG)...
June 30, 2016: Channels
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