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https://www.readbyqxmd.com/read/28937579/pyrethroids-inhibit-k2p-channels-and-activate-sensory-neurons-basis-of-insecticide-induced-paraesthesias
#1
Aida Castellanos, Alba Andres, Laura Bernal, Gerard Callejo, Nuria Comes, Arcadi Gual, Jonathan P Giblin, Carolina Roza, Xavier Gasull
Pyrethroid insecticides are widely used for pest control, in agriculture or in human public health commonly as a topical treatment for scabies and head lice. Exposure to pyrethroids such as permethrin or tetramethrin (TM) causes sensory alterations such as transient pain, burning, stinging sensations and paraesthesias. Despite the well-known effects of pyrethroids on sodium channels, actions on other channels that control sensory neuron excitability are less studied. Given the role of two-pore domain potassium (K2P) channels in modulating sensory neuron excitability and firing, both in physiological and pathological conditions, we examined the effect of pyrethroids on K2P channels mainly expressed in sensory neurons...
September 19, 2017: Pain
https://www.readbyqxmd.com/read/28936178/a-comparison-of-oral-sensory-effects-of-three-trpa1-agonists-in-young-adult-smokers-and-non-smokers
#2
Eva Ø Hansen, Lars Arendt-Nielsen, Shellie A Boudreau
This study profiled intra-oral somatosensory and vasomotor responses to three different transient receptor potential (TRP) channels, subfamily A, member 1 (TRPA1) agonists (menthol, nicotine, and cinnamaldehyde) in smoking and non-smoking young adults. Healthy non-smokers (N = 30) and otherwise healthy smokers (N = 25) participated in a randomized, double-blinded, cross-over study consisting of three experimental sessions in which they received menthol (30 mg), nicotine (4 mg), or cinnamaldehyde (25 mg) chewing gum...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28935134/sites-contributing-to-trpa1-activation-by-the-anesthetic-propofol-identified-by-photoaffinity-labeling
#3
Kellie A Woll, Kenneth A Skinner, Eleonora Gianti, Natarajan V Bhanu, Benjamin A Garcia, Vincenzo Carnevale, Roderic G Eckenhoff, Rachelle Gaudet
In addition to inducing anesthesia, propofol activates a key component of the pain pathway, the transient receptor potential ankyrin 1 ion channel (TRPA1). Recent mutagenesis studies suggested a potential activation site within the transmembrane domain, near the A-967079 cavity. However, mutagenesis cannot distinguish between protein-based and ligand-based mechanisms, nor can this site explain the complex modulation by propofol. Thus more direct approaches are required to reveal potentially druggable binding sites...
September 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28931666/trpa1-activation-in-a-human-sensory-neuronal-model-relevance-to-cough-hypersensitivity
#4
Rebecca Clarke, Kevin Monaghan, Imad About, Caoimhin S Griffin, Gerard P Sergeant, Ikhlas El Karim, J Graham McGeown, S Louise Cosby, Timothy M Curtis, Lorcan P McGarvey, Fionnuala T Lundy
The cough reflex becomes hyperresponsive in acute and chronic respiratory diseases, but understanding the underlying mechanism is hampered by difficulty accessing human tissue containing both nerve endings and neuronal cell bodies. We refined an adult stem cell sensory neuronal model to overcome the limited availability of human neurones and applied the model to study transient receptor potential ankyrin 1 (TRPA1) channel expression and activation.Human dental pulp stem cells (hDPSCs) were differentiated towards a neuronal phenotype, termed peripheral neuronal equivalents (PNEs)...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#5
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28925503/quantitative-analysis-of-mouse-dural-afferent-neurons-expressing-trpm8-vglut3-and-nf200
#6
Lynn Ren, Michelle Jaehee Chang, Zhiyu Zhang, Ajay Dhaka, Zhaohua Guo, Yu-Qing Cao
OBJECTIVE: To quantify the abundance of dural afferent neurons expressing transient receptor potential channel melastatin 8 (TRPM8), vesicular glutamate transporter 3 (VGLUT3), and neurofilament 200 (NF200) in adult mice. BACKGROUND: With the increasing use of mice as a model system to study headache mechanisms, it is important to understand the composition of dural afferent neurons in mice. In a previous study, we have measured the abundance of mouse dural afferent neurons that express neuropeptide calcitonin gene-related peptide as well as two TRP channels TRPV1 and TRPA1, respectively...
September 19, 2017: Headache
https://www.readbyqxmd.com/read/28924972/targeting-nociceptive-trp-channels-to-treat-chronic-pain-current-state-of-the-field
#7
REVIEW
Magdalene M Moran, Arpad Szallasi
Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of Transient Receptor Potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically...
September 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28919489/zinc-chloride-induced-trpa1-activation-does-not-contribute-to-toxicity-in-vitro
#8
Dirk Steinritz, Franziska Zehfuß, Bernhard Stenger, Annette Schmidt, Tanja Popp, Kai Kehe, Harald Mückter, Horst Thiermann, Thomas Gudermann
The hygroscopic zinc chloride (ZnCl2) is often used to generate smoke screens. Severe adverse pulmonary health effects have been associated with inhalation of ZnCl2 smokes. The underlying molecular toxicology is not known. Recent studies have shown that the Transient Receptor Potential Channel A1 (TRPA1) is important for sensing toxic chemicals. TRPA1 was shown to be activated by Zn(2+) which was linked to pain and inflammation. In the present study, we investigated whether TRPA1 activation contributes to ZnCl2-mediated toxicity in vitro...
September 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28912961/trpa1-expression-is-downregulated-by-dexamethasone-and-aurothiomalate-in-human-chondrocytes-trpa1-as-a-novel-factor-and-drug-target-in-arthritis
#9
Elina Nummenmaa, Mari Hämäläinen, Lauri J Moilanen, Teemu Moilanen, Katriina Vuolteenaho, Eeva Moilanen
No abstract text is available yet for this article.
2017: RMD Open
https://www.readbyqxmd.com/read/28903060/effects-of-curcumin-and-curcumin-analogues-on-trp-channels
#10
Marianna Nalli, Giorgio Ortar, Aniello Schiano Moriello, Vincenzo Di Marzo, Luciano De Petrocellis
A series of 33 curcumin analogues was synthesized and tested on TRPA1, TRPM8, and TRPV1 channels. Twenty of them acted as good modulators of TRPA1 channels. None was able to significantly activate TRPM8 channels, while curcumin itself and six curcuminoids belonging to the 1,3-dicarbonyl and acyclic series behaved as 'true' antagonists with IC50 values<5μM. Only few curcuminoids were able to modulate TRPV1 channels with EC50 and IC50 values ranging from 3.4 and 6.0μM.
September 10, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28894590/trpa1-channel-mediates-organophosphate-induced-delayed-neuropathy
#11
Qiang Ding, Sui Fang, Xueqin Chen, Youxin Wang, Jian Li, Fuyun Tian, Xiang Xu, Bernard Attali, Xin Xie, Zhaobing Gao
The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28891864/photosensitization-of-trpa1-and-trpv1-by-7-dehydrocholesterol-implications-for-the-smith-lemli-opitz-syndrome
#12
Alexandru Babes, Cosmin I Ciotu, Tal Hoffmann, Tatjana I Kichko, Tudor Selescu, Cristian Neacsu, Susanne K Sauer, Peter W Reeh, Michael J M Fischer
Loss of function mutations in the enzyme 7-dehydrocholesterol reductase are responsible for the Smith-Lemli-Opitz syndrome, in which 7-dehydrocholesterol (7-DHC) levels are markedly increased in the plasma and tissues of patients. This increase in 7-DHC is probably associated with the painful and itchy photosensitivity reported by the large majority of Smith-Lemli-Opitz syndrome patients. In order to identify the molecular targets involved in the activation and photosensitization of primary afferents by 7-DHC we focused on TRPA1 and TRPV1, two ion channels expressed in nociceptive nerve endings and previously shown to respond to ultraviolet and visible light under pathophysiological circumstances...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28884838/review-article-transient-receptor-potential-channels-as-possible-therapeutic-targets-in-irritable-bowel-syndrome
#13
REVIEW
A B Beckers, Z Z R M Weerts, Z Helyes, A A M Masclee, D Keszthelyi
BACKGROUND: Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well...
September 8, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28884307/the-role-of-the-transient-receptor-potential-ankyrin-type-1-trpa1-channel-in-migraine-pain-evaluation-in-an-animal-model
#14
Chiara Demartini, Cristina Tassorelli, Anna Maria Zanaboni, Germana Tonsi, Oscar Francesconi, Cristina Nativi, Rosaria Greco
BACKGROUND: Clinical and experimental studies have pointed to the possible involvement of the transient receptor potential ankyrin type-1 (TRPA1) channels in migraine pain. In this study, we aimed to further investigate the role of these channels in an animal model of migraine using a novel TRPA1 antagonist, ADM_12, as a probe. METHODS: The effects of ADM_12 on nitroglycerin-induced hyperalgesia at the trigeminal level were investigated in male rats using the quantification of nocifensive behavior in the orofacial formalin test...
September 7, 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28869563/synergic-anti-pruritus-mechanisms-of-action-for-the-radix-sophorae-flavescentis-and-fructus-cnidii-herbal-pair
#15
Jiali Zhong, Zhihong Liu, Xinxin Zhou, Jun Xu
Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the main active ingredients for the RSF and FC herbal pair. We demonstrate that the RSF-FC herbal pair can be elucidated by mining the chemical structures of compounds derived from RSF and FC. Based on chemical structure data, the putative targets for RSF and FC were predicted...
September 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28845027/dibutyl-phthalate-rather-than-monobutyl-phthalate-facilitates-contact-hypersensitivity-to-fluorescein-isothiocyanate-in-a-mouse-model
#16
Kohta Kurohane, Kota Sekiguchi, Erina Ogawa, Masato Tsutsumi, Yasuyuki Imai
Dibutyl phthalate (DBP) is a plasticizer used for many consumer products including cosmetics. Potential health concerns regarding DBP include reproductive and developmental toxicity, endocrine disruption and neurotoxicity. DBP is a high priority chemical as to reduction of exposure of children to it. Through reproductive toxicity studies, monobutyl phthalate (MBP) has been proposed to be the active metabolite derived from DBP. We previously demonstrated that DBP activates transient receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory neurons...
August 26, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#17
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826482/anti-nociceptive-action-of-peripheral-mu-opioid-receptors-by-g-beta-gamma-protein-mediated-inhibition-of-trpm3-channels
#18
Sandeep Dembla, Marc Behrendt, Florian Mohr, Christian Goecke, Julia Sondermann, Franziska M Schneider, Marlene Schmidt, Julia Stab, Raissa Enzeroth, Michael G Leitner, Paulina Nuñez-Badinez, Jochen Schwenk, Bernd Nürnberg, Alejandro Cohen, Stephan E Philipp, Wolfgang Greffrath, Moritz Bünemann, Dominik Oliver, Eleonora Zakharian, Manuela Schmidt, Johannes Oberwinkler
Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful analgesia. The cellular mechanisms downstream of peripheral µORs are not well understood. Here, we show in neurons of murine dorsal root ganglia that pro-nociceptive TRPM3 channels, present in the peripheral parts of nociceptors, are strongly inhibited by µOR activation, much more than other TRP channels in the same compartment, like TRPV1 and TRPA1...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#19
Holger Beckmann, Julia Richter, Kerstin Hill, Nicole Urban, Horst Lemoine, Michael Schaefer
The transient receptor potential canonical channel 5 (TRPC5) is a Ca(2+)-permeable ion channel, which is predominantly expressed in the brain. TRPC5-deficient mice exhibit a reduced innate fear response and impaired motor control. In addition, outgrowth of hippocampal and cerebellar neurons is retarded by TRPC5. However, pharmacological evidence of TRPC5 function on cellular or organismic levels is sparse. Thus, there is still a need for identifying novel and efficient TRPC5 channel modulators. We, therefore, screened compound libraries and identified the glucocorticoid methylprednisolone and N-[3-(adamantan-2-yloxy)propyl]-3-(6-methyl-1,1-dioxo-2H-1λ(6),2,4-benzothiadiazin-3-yl)propanamide (BTD) as novel TRPC5 activators...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28805980/an-environmental-pollutant-9-10-phenanthrenequinone-activates-human-trpa1-via-critical-cysteines-621-and-665
#20
Katsuhiko Muraki, Takashi Sekine, Yuna Ando, Hiroka Suzuki, Noriyuki Hatano, Tadashi Hirata, Yukiko Muraki
Transient receptor potential ankyrin 1 (TRPA1) is activated by noxious cold, mechanical stimulation, and irritant chemicals. In our recent study, 9, 10-phenanthrenequinone (9,10-PQ) is the most potent irritant for activation of NRF2 among 1395 cigarette smoke components and it may be, therefore, important to find its additional targets. Here, we show that 9,10-PQ functions as an activator of TRPA1 in human embryonic kidney (HEK) cells expressing human wild-type TRPA1 (HEK-wTRPA1) and human alveolar A549 (A549) cells...
August 2017: Pharmacology Research & Perspectives
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