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https://www.readbyqxmd.com/read/29150643/%C3%AE-eudesmol-an-oxygenized-sesquiterpene-stimulates-appetite-via-trpa1-and-the-autonomic-nervous-system
#1
Kazuaki Ohara, Takafumi Fukuda, Yuko Ishida, Chika Takahashi, Rena Ohya, Mikio Katayama, Kunitoshi Uchida, Makoto Tominaga, Katsuya Nagai
Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#2
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29131007/proteinase-activated-receptor-2-sensitivity-of-amplified-trpa1-activity-in-skeletal-muscle-afferent-nerves-and-exercise-pressor-reflex-in-rats-with-femoral-artery-occlusion
#3
Jihong Xing, Jianhua Li
BACKGROUND/AIMS: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129206/differential-cytotoxicity-and-intracellular-calcium-signalling-following-activation-of-the-calcium-permeable-ion-channels-trpv1-and-trpa1
#4
Thomas Stueber, Mirjam J Eberhardt, Yaki Caspi, Shaya Lev, Alexander Binshtok, Andreas Leffler
Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29121401/mp29-02-reduces-nasal-hyperreactivity-and-nasal-mediators-in-patients-with-house-dust-mite-allergic-rhinitis
#5
Inge Kortekaas Krohn, Ina Callebaut, Yeranddy A Alpizar, Brecht Steelant, Laura Van Gerven, Per Stahl Skov, Ahmad Kasran, Karel Talavera, Mira M Wouters, Jan L Ceuppens, Sven F Seys, Peter W Hellings
BACKGROUND: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate (FP)) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. METHODS: A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR...
November 9, 2017: Allergy
https://www.readbyqxmd.com/read/29111112/anti-migraine-effect-of-%C3%A2-9-tetrahydrocannabinol-in-the-female-rat
#6
Ram Kandasamy, Cole T Dawson, Rebecca M Craft, Michael M Morgan
Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆(9)-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat. Microinjection of the TRPA1 agonist allyl isothiocyanate (AITC) onto the dura mater produced migraine-like pain for 3h as measured by depression of home cage wheel running...
October 28, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29102918/non-steroidal-anti-inflammatory-drugs-attenuate-agonist-evoked-activation-of-transient-receptor-potential-channels
#7
M G Tsagareli, I Nozadze, N Tsiklauri, G Gurtskaia
Transient receptor potential (TRP) cation channels are the largest group of sensory detector proteins expressed in the nerve terminals of many receptors including nociceptors, and are activated by temperature and chemicals that elicit hot or cold sensations. Antagonists of these channels are likely promising targets for new analgesic drugs at the peripheral and central levels. Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we investigated whether three widely used NSAIDs (diclofenac, ketorolac, and xefocam) affect thermal and mechanical hyperalgesia following the activation of TRPA1 and TRPV1 channels...
November 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#8
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29094727/a-pivotal-role-for-the-activation-of-trpv3-channel-in-itch-sensations-induced-by-the-natural-skin-sensitizer-carvacrol
#9
Ting-Ting Cui, Gong-Xin Wang, Ning-Ning Wei, KeWei Wang
Itching is an intricate, common symptom of dermatologic and systemic diseases, and both TRPV3 and TRPA1 channels have been suggested to function as downstream effector targets. But the relative contributions of TRPV3 and TRPA1 to itch sensation in vivo remain unclear. To dissect the role of TRPA1 or TRPV3 in the cutaneous sensation of itching, we took the advantage of a natural compound carvacrol from oregano, and examined its effect on the induction of scratching behavior in mice. We showed that the intradermal injection of carvacrol (0...
November 2, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29092846/bdnf-overexpression-in-bladder-induces-neuronal-changes-to-mediate-bladder-overactivity
#10
Mahendra Kashyap, Subrata Pore, William C de Groat, Christopher Chermansky, Naoki Yoshimura, Pradeep Tyagi
Elevated levels of brain derived neurotrophic factor (BDNF) in urine of overactive bladder (OAB) patients support the association of BDNF with OAB symptoms, but the causality is not known. Here, we investigated the functionality of BDNF overexpression in rat bladder following bladder wall transfection of either BDNF or luciferase transgenes (10µg). A week after transfection, BDNF overexpression in bladder tissue and elevation of urine BDNF levels was observed together with increased transcript of BDNF, its cognate receptors (TrkB & p75NTR) and downstream PLCγ isoforms in bladder...
November 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29084244/trpa1-activation-in-peripheral-sensory-neurons-underlies-the-ionic-basis-of-pain-hypersensitivity-in-response-to-vinca-alkaloids
#11
Nina Boiko, Geraldo Medrano, Elizabeth Montano, Nan Jiang, Claire R Williams, Ngonidzashe B Madungwe, Jean C Bopassa, Charles C Kim, Jay Z Parrish, Kenneth M Hargreaves, James D Stockand, Benjamin A Eaton
Chemotherapy induced peripheral neuropathy (CIPN), a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described...
2017: PloS One
https://www.readbyqxmd.com/read/29081531/sensory-trp-channels-contribute-differentially-to-skin-inflammation-and-persistent-itch
#12
Jing Feng, Pu Yang, Madison R Mack, Dariia Dryn, Jialie Luo, Xuan Gong, Shenbin Liu, Landon K Oetjen, Alexander V Zholos, Zhinan Mei, Shijin Yin, Brian S Kim, Hongzhen Hu
Although both persistent itch and inflammation are commonly associated with allergic contact dermatitis (ACD), it is not known if they are mediated by shared or distinct signaling pathways. Here we show that both TRPA1 and TRPV1 channels are required for generating spontaneous scratching in a mouse model of ACD induced by squaric acid dibutylester (SADBE), a small molecule hapten, through directly promoting the excitability of pruriceptors. TRPV1 but not TRPA1 channels protect the skin inflammation, as genetic ablation of TRPV1 function or pharmacological ablation of TRPV1-positive sensory nerves promotes cutaneous inflammation in the SADBE-induced ACD...
October 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/29081457/an-aliphatic-ester-diisopropyl-sebacate-exhibited-an-adjuvant-effect-on-fluorescein-isothiocyanate-induced-contact-hypersensitivity-mouse-models
#13
Kohta Kurohane, Ayako Kimura, Rie Terasawa, Kamiyu Kobayashi, Wakana Suzuki, Takeshi Matsuoka, Yasuyuki Imai
Alternative plasticizers have become more popular due to health concerns about phthalate esters. We demonstrated that phthalate esters enhanced skin sensitization to fluorescein isothiocyanate (FITC) in mouse contact hypersensitivity models. Alternative plasticizers have not been well studied as to their effect on the immune system. We previously found that diisopropyl adipate (DIPA), an aliphatic dicarboxylic acid ester, enhanced skin sensitization to FITC. Sebacate esters are also widely used as alternative plasticizers...
October 27, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29054683/the-anthelminthic-drug-praziquantel-is-a-selective-agonist-of-the-sensory-transient-receptor-potential-melastatin-type-8-channel
#14
Ramona-Madalina Babes, Tudor Selescu, Dan Domocos, Alexandru Babes
Praziquantel is the most effective anthelminthic drug for the treatment of schistosomiasis, an infectious disease caused by the platyhelminth Schistosoma mansoni. While praziquantel is known to trigger calcium influx into schisostomes, followed by spastic paralysis of the worms and tegumental disruption, the mechanism of action of the drug is not completely understood. Although relatively well tolerated, praziquantel has been reported to cause mild adverse effects, including nausea, abdominal pain and headaches...
October 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29048889/lipoyl-homotaurine-derivative-adm_12-reverts-oxaliplatin-induced-neuropathy-and-reduces-cancer-cells-malignancy-by-inhibiting-carbonic-anhydrase-ix-caix
#15
Marco Fragai, Giuseppina Comito, Lorenzo Di Cesare Mannelli, Roberta Gualdani, Vito Calderone, Alexandra Louka, Barbara Richichi, Oscar Francesconi, Andrea Angeli, Alessio Nocentini, Paola Gratteri, Paola Chiarugi, Carla Ghelardini, Francesco Tadini-Buoninsegni, Claudiu T Supuran, Cristina Nativi
Oxaliplatin (OXA) is a valuable and largely used cancer drug which induces a serious and intractable neuropathy. The lipoyl-homotaurine derivative (ADM_12) reverts in vivo OXA-induced neuropathy, and it is an effective antagonist of the nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a synergy with OXA in vitro and proved to inhibit CA IX, a relevant therapeutic target, clearly interfering with pancreatic cancer cells' aggressiveness.
October 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29048608/zebrafish-locomotor-responses-reveal-irritant-effects-of-fine-pm-extracts-and-a-role-for-trpa1
#16
Joey S Stevens, Stephanie Padilla, David M DeMarini, Deborah L Hunter, W Kyle Martin, Leslie C Thompson, M Ian Gilmour, Mehdi S Hazari, Aimen K Farraj
Exposure to fine particulate matter (PM) air pollution causes adverse cardiopulmonary outcomes. Yet the limited capacity to readily identify contributing PM sources and associated PM constituents in any given ambient air shed impedes risk assessment efforts. The health effects of PM have been attributed in part to its capacity to elicit irritant responses. A variety of chemicals trigger irritant behavior responses in zebrafish that can be easily measured. The purposes of this study were to examine the utility of zebrafish locomotor responses in the toxicity assessment of fine PM and its chemical fractions and uncover mechanisms of action...
October 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29038531/trpa1-fgfr2-binding-event-is-a-regulatory-oncogenic-driver-modulated-by-mirna-142-3p
#17
Jonathan Berrout, Eleni Kyriakopoulou, Lavanya Moparthi, Alexandra S Hogea, Liza Berrout, Cristina Ivan, Mihaela Lorger, John Boyle, Chris Peers, Stephen Muench, Jacobo Elies Gomez, Xin Hu, Carolyn Hurst, Thomas Hall, Sujanitha Umamaheswaran, Laura Wesley, Mihai Gagea, Michael Shires, Iain Manfield, Margaret A Knowles, Simon Davies, Klaus Suhling, Yurema Teijeiro Gonzalez, Neil Carragher, Kenneth Macleod, N Joan Abbott, George A Calin, Nikita Gamper, Peter M Zygmunt, Zahra Timsah
Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29038158/activation-of-human-transient-receptor-potential-melastatin-8-trpm8-by-calcium-rich-particulate-materials-and-effects-on-human-lung-cells
#18
John G Lamb, Erin G Romero, Zhenyu Lu, Seychelle K Marcus, Hannah C Peterson, John M Veranth, Cassandra E Deering-Rice, Christopher A Reilly
To better understand how adverse health effects are caused by particulate materials, and to develop preventative measures, it is important to identify the properties of particles and proteins that link exposure with specific biological outcomes. Coal fly ash (CFA) is a by-product of coal combustion that can affect human health. Here we show that human transient receptor potential melastatin-8 (TRPM8) and an N-terminally truncated TRPM8 variant (TRPM8-Δ801) are activated by CFA and calcium-rich nanoparticles and/or soluble salts within CFA...
October 16, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29037810/chemical-and-thermal-sensitivity-of-medaka-trpa1-analyzed-in-heterologous-expression-system
#19
Mai Oda, Kan Saito, Shun Hatta, Yoshihiro Kubo, Osamu Saitoh
TRPA1 of insects and several tetrapod vertebrates except for those of rodents have been reported to be activated by noxious chemicals and also by high temperature with a relatively clear threshold. We previously analyzed the characteristics of two TRPA1 paralogs of zebrafish (zTRPA1a, b) and demonstrated that zTRPA1a is specialized for chemical sensing while zTRPA1b responds to thermal stimulations, that zTRPA1b responds to both cold and heat stimuli, and that heat stimulation gradually activates zTRPA1b without a clear threshold...
October 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29034461/the-migraine-attack-as-a-homeostatic-neuroprotective-response-to-brain-oxidative-stress-preliminary-evidence-for-a-theory
#20
Jonathan M Borkum
BACKGROUND: Previous research has suggested that migraineurs show higher levels of oxidative stress (lipid peroxides) between migraine attacks and that migraine triggers may further increase brain oxidative stress. Oxidative stress is transduced into a neural signal by the TRPA1 ion channel on meningeal pain receptors, eliciting neurogenic inflammation, a key event in migraine. Thus, migraines may be a response to brain oxidative stress. RESULTS: In this article, a number of migraine components are considered: cortical spreading depression, platelet activation, plasma protein extravasation, endothelial nitric oxide synthesis, and the release of serotonin, substance P, calcitonin gene-related peptide, and brain-derived neurotrophic factor...
October 16, 2017: Headache
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