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https://www.readbyqxmd.com/read/27904941/trpa1-substance-p-histamine-and-5-hydroxytryptamine-interact-in-an-interdependent-way-to-induce-nociception
#1
Luana Fischer, Maria Isabel Lavoranti, Mariana de Oliveira Borges, Alana Farias Miksza, Natalia Fantin Sardi, Bruno Jacson Martynhak, Claudia H Tambeli, Carlos Amílcar Parada
BACKGROUND: Although TRPA1, SP, histamine and 5-hydroxytryptamine (5-HT) have recognized contribution to nociceptive mechanisms, little is known about how they interact with each other to mediate inflammatory pain in vivo. In this study we evaluated whether TRPA1, SP, histamine and 5-HT interact, in an interdependent way, to induce nociception in vivo. METHODS AND RESULTS: The subcutaneous injection of the TRPA1 agonist allyl isothiocyanate (AITC) into the rat's hind paw induced a dose-dependent and short lasting behavioral nociceptive response that was blocked by the co-administration of the TRPA1 antagonist, HC030031, or by the pretreatment with antisense ODN against TRPA1...
November 30, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27900410/-%C3%AE-bisabolol-reduces-orofacial-nociceptive-behavior-in-rodents
#2
Luana Torres Melo, Mariana Araújo Braz Duailibe, Luciana Moura Pessoa, Flávio Nogueira da Costa, Antonio Eufrásio Vieira-Neto, Ana Paula de Vasconcellos Abdon, Adriana Rolim Campos
The purposes of this study were to evaluate the anti-nociceptive effect of oral and topical administration of (-)-α-bisabolol (BISA) in rodent models of formalin- or cinnamaldehyde-induced orofacial pain and to explore the inhibitory mechanisms involved. Orofacial pain was induced by injecting 1.5% formalin into the upper lip of mice (20 μL) or into the temporomandibular joint (TMJ) of rats (50 μL). In another experiment, orofacial pain was induced with cinnamaldehyde (13.2 μg/lip). Nociceptive behavior was proxied by time (s) spent rubbing the injected area and by the incidence of head flinching...
November 29, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27899696/selective-antagonism-of-trpa1-produces-limited-efficacy-in-models-of-inflammatory-and-neuropathic-induced-mechanical-hypersensitivity-in-rats
#3
Sonya G Lehto, Andy D Weyer, Beth D Youngblood, Maosheng Zhang, Ruoyuan Yin, Weiya Wang, Yohannes Teffera, Melanie Cooke, Cheryl L Stucky, Laurie Schenkel, Stephanie Geuns-Meyer, Bryan D Moyer, Kenneth D Wild, Narender R Gavva
The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27876485/cannabinoid-receptors-and-trpa1-on-neuroprotection-in-a-model-of-retinal-ischemia
#4
D S M Araújo, V S Miya-Coreixas, P Pandolfo, K C Calaza
Retinal ischemia is a pathological event present in several retinopathies such as diabetic retinopathy and glaucoma, leading to partial or full blindness with no effective treatment available. Since synthetic and endogenous cannabinoids have been studied as modulators of ischemic events in the central nervous system (CNS), the present study aimed to investigate the involvement of cannabinoid system in the cell death induced by ischemia in an avascular (chick) retina. We observed that chick retinal treatment with a combination of WIN 55212-2 and cannabinoid receptor antagonists (either AM251/O-2050 or AM630) decreased the release of lactate dehydrogenase (LDH) induced by retinal ischemia in an oxygen and glucose deprivation (OGD) model...
November 19, 2016: Experimental Eye Research
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
#5
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/27874100/structural-basis-of-trpa1-inhibition-by-hc-030031-utilizing-species-specific-differences
#6
Rupali Gupta, Shigeru Saito, Yoshiharu Mori, Satoru G Itoh, Hisashi Okumura, Makoto Tominaga
Pain is a harmful sensation that arises from noxious stimuli. Transient receptor potential ankyrin 1 (TRPA1) is one target for studying pain mechanisms. TRPA1 is activated by various stimuli such as noxious cold, pungent natural products and environmental irritants. Since TRPA1 is an attractive target for pain therapy, a few TRPA1 antagonists have been developed and some function as analgesic agents. The responses of TRPA1 to agonists and antagonists vary among species and these species differences have been utilized to identify the structural basis of activation and inhibition mechanisms...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864675/drugs-affecting-trp-channels
#7
M A Wortley, M A Birrell, M G Belvisi
Chronic obstructive pulmonary disease (COPD) and asthma are both common respiratory diseases that are associated with airflow reduction/obstruction and pulmonary inflammation. Whilst drug therapies offer adequate symptom control for many mild to moderate asthmatic patients, severe asthmatics and COPD patients symptoms are often not controlled, and in these cases, irreversible structural damage occurs with disease progression over time. Transient receptor potential (TRP) channels, in particular TRPV1, TRPA1, TRPV4 and TRPM8, have been implicated with roles in the regulation of inflammation and autonomic nervous control of the lungs...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27852962/anatomy-and-immunochemical-characterization-of-the-non-arterial-peptidergic-diffuse-dural-innervation-of-the-rat-and-rhesus-monkey-implications-for-functional-regulation-and-treatment-in-migraine
#8
Frank L Rice, Jennifer Y Xie, Phillip J Albrecht, Emily Acker, Justin Bourgeois, Edita Navratilova, David W Dodick, Frank Porreca
OBJECTIVE: The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. METHODS: We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey...
November 16, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27835802/transient-receptor-potential-channels-in-neuropathic-pain
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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/27799370/intracellular-trpa1-mediates-ca2-release-from-lysosomes-in-dorsal-root-ganglion-neurons
#16
Shujiang Shang, Feipeng Zhu, Bin Liu, Zuying Chai, Qihui Wu, Meiqin Hu, Yuan Wang, Rong Huang, Xiaoyu Zhang, Xi Wu, Lei Sun, Yeshi Wang, Li Wang, Huadong Xu, Sasa Teng, Bing Liu, Lianghong Zheng, Chen Zhang, Fukang Zhang, Xinghua Feng, Desheng Zhu, Changhe Wang, Tao Liu, Michael X Zhu, Zhuan Zhou
Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca(2+) concentration ([Ca(2+)]i) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca(2+) Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes...
November 7, 2016: Journal of Cell Biology
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/27792844/hydrogen-peroxide-preferentially-activates-capsaicin-sensitive-high-threshold-afferents-via-trpa1-channels-in-the-guinea-pig-bladder
#18
S Nicholas, S Y Yuan, S J H Brookes, N J Spencer, V P Zagorodnyuk
BACKGROUND AND PURPOSE: There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2 O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. EXPERIMENTAL APPROACH: 'Close-to-target' single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro...
October 28, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27779810/trpa1-gene-polymorphisms-and-childhood-asthma
#19
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/27779479/pronociceptive-effects-induced-by-cutaneous-application-of-a-transient-receptor-potential-ankyrin-1-trpa1-channel-agonist-methylglyoxal-in-diabetic-animals-comparison-with-tunicamycin-induced-endoplastic-reticulum-stress
#20
H Viisanen, H Chapman, H Wei, M Lasierra Losada, A Koivisto, K E Akerman, A Pertovaara
Methylglyoxal (MG) is a reactive carbonyl compound generated in diabetes mellitus. MG is an established transient receptor potential ankyrin 1 (TRPA1) channel agonist that contributes to TRPA1-mediated diabetic pain hypersensitivity. Here we studied whether exposure to diabetes and thereby to elevated endogenous MG modulates hypersensitivity induced by intradermal MG. Moreover, since diabetes induces endoplasmic reticulum (ER) stress, we compared the role of TRPA1 in diabetes and ER stress by assessing whether tunicamycin-induced ER stress, without diabetes, produces TRPA1-mediated pain hypersensitivity and by assessing whether ER stress and diabetes have similar modulatory effects on MG-induced hypersensitivity...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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