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https://www.readbyqxmd.com/read/28225032/4-isopropylcyclohexanol-has-potential-analgesic-effects-through-the-inhibition-of-anoctamin-1-trpv1-and-trpa1-channel-activities
#1
Yasunori Takayama, Hidemasa Furue, Makoto Tominaga
Interactions between calcium-activated chloride channel anoctamin 1 (ANO1) and transient receptor potential vanilloid 1 (TRPV1) enhance pain sensations in mice, suggesting that ANO1 inhibition could have analgesic effects. Here we show that menthol and the menthol analogue isopropylcyclohexane (iPr-CyH) inhibited ANO1 channels in mice. The iPr-CyH derivative 4-isopropylcyclohexanol (4-iPr-CyH-OH) inhibited mouse ANO1 currents more potently than iPr-CyH. Moreover, 4-iPr-CyH-OH inhibited the activities of TRPV1, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8) and TRPV4...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220825/notch1-promoted-trpa1-expression-in-erythroleukemic-cells-suppresses-erythroid-but-enhances-megakaryocyte-differentiation
#2
Ji-Lin Chen, Yueh-Hsin Ping, Min-Jen Tseng, Yuan-I Chang, Hsin-Chen Lee, Rong-Hong Hsieh, Tien-Shun Yeh
The Notch1 pathway plays important roles in modulating erythroid and megakaryocyte differentiation. To screen the Notch1-related genes that regulate differentiation fate of K562 and HEL cells, the expression of transient receptor potential ankyrin 1 (TRPA1) was induced by Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor. N1IC and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1) bound to TRPA1 promoter region to regulate transcription in K562 cells. Transactivation of TRPA1 promoter by N1IC depended on the methylation status of TRPA1 promoter...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217875/mechanisms-of-pruritogen-induced-activation-of-itch-nerves-in-isolated-mouse-skin
#3
F Ru, H Sun, D Jurcakova, R A Herbstsomer, J Meixong, X Dong, B J Undem
Chloroquine (CQ) and histamine are pruritogens commonly used to study itch in the mouse. A novel skin-nerve preparation was used to evaluate chloroquine (CQ)- and histamine- induced activation of afferent nerves in the dorsal thoracic skin of the mouse. All CQ sensitive nerves were C-fibres, and were also sensitive to histamine. The response to CQ, but not histamine, was largely absent in mrgpr cluster Δ -/- mice supporting the hypothesis that CQ evokes itch largely via stimulation of MrgprA3 receptors. The CQ-induced action potential discharge was largely absent in phospholipase Cβ3 knockout animals...
February 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28215745/astrocyte-transport-of-glutamate-and-neuronal-activity-reciprocally-modulate-tau-pathology-in-drosophila
#4
Jason G Kilian, Heng-Wei Hsu, Kenneth Mata, Fred W Wolf, Masashi Kitazawa
Abnormal buildup of the microtubule associated protein tau is a major pathological hallmark of SAlzheimer's disease (AD)and various tauopathies. The mechanisms by which pathological tau accumulates and spreads throughout the brain remain largely unknown. Previously, we demonstrated that a restoration of the major astrocytic glutamate transporter, GLT1, ameliorated a buildup of tau pathology and rescued cognition in a mouse model of AD. We hypothesized thataberrant extracellular glutamate and abnormal neuronal excitatory activities promoted tau pathology...
February 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28213106/oral-treatment-with-essential-oil-of-hyptis-spicigera-lam-lamiaceae-reduces-acute-pain-and-inflammation-in-mice-potential-interactions-with-transient-receptor-potential-trp-ion-channels
#5
Róli Rodrigues Simões, Igor Dos Santos Coelho, Stella Célio Junqueira, Glauce Regina Pigatto, Marcos José Salvador, Adair Roberto Soares Santos, Felipe Meira de Faria
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. AIM OF THE STUDY: The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. MATERIAL AND METHODS: The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28197074/the-first-extracellular-linker-is-important-for-several-aspects-of-the-gating-mechanism-of-human-trpa1-channel
#6
Lenka Marsakova, Ivan Barvik, Vlastimil Zima, Lucie Zimova, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28194754/requirement-of-extracellular-ca-2-binding-to-specific-amino-acids-for-heat-evoked-activation-of-trpa1
#7
Erkin Kurganov, Shigeru Saito, Claire T Saito, Makoto Tominaga
Transient receptor potential ankyrin 1 (TRPA1) is a homotetrameric nonselective cation-permeable channel that has six transmembrane domains and cytoplasmic N- and C-termini. The N-terminus is characterized by an unusually large number of ankyrin repeats. Although the 3-dimensional structure of human TRPA1 has been determined, and TRPA1 channels from insects to birds are known to be activated by heat stimulus, the mechanism for temperature-dependent TRPA1 activation is unclear. We previously reported that extracellular Ca(2+) , but not intracellular Ca(2+) , plays an important role in heat-evoked TRPA1 activation in green anole lizards (gaTRPA1)...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28187208/respiratory-virus-infection-up-regulates-trpv1-trpa1-and-asics3-receptors-on-airway-cells
#8
Shadia Omar, Rebecca Clarke, Haniah Abdullah, Clare Brady, John Corry, Hanagh Winter, Olivier Touzelet, Ultan F Power, Fionnuala Lundy, Lorcan P A McGarvey, S Louise Cosby
Receptors implicated in cough hypersensitivity are transient receptor potential vanilloid 1 (TRPV1), transient receptor potential cation channel, Subfamily A, Member 1 (TRPA1) and acid sensing ion channel receptor 3 (ASIC3). Respiratory viruses, such as respiratory syncytial virus (RSV) and measles virus (MV) may interact directly and/or indirectly with these receptors on sensory nerves and epithelial cells in the airways. We used in vitro models of sensory neurones (SHSY5Y or differentiated IMR-32 cells) and human bronchial epithelium (BEAS-2B cells) as well as primary human bronchial epithelial cells (PBEC) to study the effect of MV and RSV infection on receptor expression...
2017: PloS One
https://www.readbyqxmd.com/read/28181685/effects-of-estrogen-receptor-%C3%AE-stimulation-in-a-rat-model-of-non-bacterial-prostatic-inflammation
#9
Shinsuke Mizoguchi, Kenichi Mori, Zhou Wang, Teresa Liu, Yasuhito Funahashi, Fuminori Sato, Donald B DeFranco, Naoki Yoshimura, Hiromitsu Mimata
BACKGROUND: There is increasing evidence showing that chronic non-bacterial prostatic inflammation is involved in the pathogenesis of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS). It has also been reported that estrogen receptor β (ERβ) could have an immunoprotective role in prostatic tissue. Therefore, we investigated the effect of ERβ-activation on not only prostatic inflammation, but also bladder overactive conditions in a rat model with nonbacterial prostatic inflammation...
February 9, 2017: Prostate
https://www.readbyqxmd.com/read/28176353/lysophosphatidic-acid-induced-itch-is-mediated-by-signaling-of-lpa5-receptor-phospholipase-d-and-trpa1-trpv1
#10
Hiroki Kittaka, Kunitoshi Uchida, Naomi Fukuta, Makoto Tominaga
Intractable and continuous itch sensations often accompany diseases such as atopic dermatitis, neurogenic lesions, uremia and cholestasis. Lysophosphatidic acid (LPA) is an itch mediator found in cholestatic itch patients and it induces acute itch and pain in the experimental rodent models. However, the molecular mechanism by which LPA activates peripheral sensory neurons remains unknown. In this study, we used a cheek injection method in mice to reveal that LPA induced itch-related behaviors but not pain-related behaviors...
February 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28162534/-297-ngf-and-cnp-induce-mechanical-hypersensitivity-and-hyperalgesic-priming-through-distinct-signaling-mechanisms-converging-on-trpv1-and-trpa1-channels
#11
A Shepherd, A Tiwari, L Loo, S Kadunganattil, D Mohapatra
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28162523/-289-angiotensin-ii-causes-mechanical-hypersensitivity-via-macrophage-derived-ros-production-and-activation-of-trpa1
#12
A Shepherd, D Mohapatra
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28137611/analgesic-effect-of-dimethyl-trisulfide-in-mice-is-mediated-by-trpa1-and-sst4-receptors
#13
Gábor Pozsgai, Maja Payrits, Éva Sághy, Réka Sebestyén-Bátai, Elise Steen, Éva Szőke, Zoltán Sándor, Margit Solymár, András Garami, Péter Orvos, László Tálosi, Zsuzsanna Helyes, Erika Pintér
TRPA1 receptors are calcium-permeable ligand-gated channels expressed in primary sensory neurons and involved in inflammation and pain. Activation of these neurons might have analgesic effect. Suggested mechanism of analgesic effect mediated by TRPA1 activation is the release of somatostatin (SOM) and its action on sst4 receptors. In the present study analgesic effect of TRPA1 activation on primary sensory neurons by organic trisulfide compound dimethyl trisulfide (DMTS) presumably leading to SOM release was investigated...
January 28, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28130183/thiazolidine-reacts-with-thioreactive-biomolecules
#14
Deyuan Su, Yin Nian, Fenglei Zhang, Jinsheng Hu, Jianmin Cui, Ming Zhou, Jian Yang, Shu Wang
The thiazolidine ring is a biologically active chemical structure and is associated with many pharmacological activities. However, the biological molecules that can interact with the thiazolidine ring are not known. We show that thiazolidine causes sustained activation of the TRPA1 channel and chemically reacts with glutathione, and the chemical reactivity of thiazolidine ring is required for TRPA1 activation. Reducing agents reverse thiazolidine-induced TRPA1 activation, and mutagenesis studies show that nucleophilic cysteine residues in TRPA1 are critical, suggesting an activation mechanism involving thioreactive chemical reactions...
January 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28126501/hyperalgesic-and-hypoalgesic-mechanisms-evoked-by-the-acute-administration-of-ccl5-in-mice
#15
Sara González-Rodríguez, Miguel G Álvarez, Mario García-Domínguez, Ana Lastra, Rafael Cernuda-Cernuda, Alicia R Folgueras, María Teresa Fernández-García, Agustín Hidalgo, Ana Baamonde, Luis Menéndez
We show here that the intraplantar administration of CCL5 in mice produces hyperalgesia at low doses but activates compensatory antinociceptive mechanisms at doses slightly higher. Thus, the injection of 3-10 ng of CCL5 evoked thermal hyperalgesia through the activation of CCR1 and CCR5 receptors, as demonstrated by the inhibitory effect exerted by the selective antagonists J113863 (0.01-0.1 μg) and DAPTA (0.3-3 μg), respectively. The prevention of this hyperalgesia by diclofenac (1-10 μg), the inhibitors of COX-1 SC-560 (0...
January 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28118665/functional-properties-of-sensory-nerve-terminals-of-the-mouse-cornea
#16
Omar González-González, Federico Bech, Juana Gallar, Jesús Merayo-Lloves, Carlos Belmonte
Purpose: To define the firing properties of sensory nerve terminals innervating the adult mouse cornea in response to external stimuli of differing modality. Methods: Extracellular electrical activity of single corneal sensory nerve terminals was recorded in excised eyes of C57BL/6J mice. Eyes were placed in a recording chamber and were continuously superfused with warm saline solution. Nerve terminal impulse (NTI) activity was recorded by means of a glass pipette (tip ∼ 50 μm), applied on the corneal surface...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28106998/identification-of-cyclic-depsipeptides-and-their-dedicated-synthetase-from-hapsidospora-irregularis
#17
Shuwei Zhang, Yixing Qiu, Thomas B Kakule, Zhenyu Lu, Fuchao Xu, John G Lamb, Christopher A Reilly, Yong Zheng, Shing Wo Simon Sham, Wei Wang, Lijiang Xuan, Eric W Schmidt, Jixun Zhan
Seven cyclic depsipeptides were isolated from Hapsidospora irregularis and structurally characterized as the calcium channel blocker leualacin and six new analogues based on the NMR and HRESIMS data. These new compounds were named leualacins B-G. The absolute configurations of the amino acids and 2-hydroxyisocaproic acids were determined by recording the optical rotation values. Biological studies showed that calcium influx elicited by leualacin F in primary human lobar bronchial epithelial cells involves the TRPA1 channel...
January 20, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28103292/muscle-reactive-oxygen-species-ros-contribute-to-post-incisional-guarding-via-the-trpa1-receptor
#18
Daisuke Sugiyama, Sinyoung Kang, Timothy J Brennan
BACKGROUND: Deep tissues and their afferents have unique responses to various stimuli and respond to injury distinctively. However, the types of receptors and endogenous ligands that have a key role in pain after deep tissue incision are unknown. TRPA1 has been shown to mediate pain-related responses in inflammation- and nerve injury-induced pain models. We hypothesized that TRPA1 has an important role in pain behaviors after deep tissue incision. METHODS: The effect of various doses of intraperitoneal (i...
2017: PloS One
https://www.readbyqxmd.com/read/28102732/exacerbating-effects-of-pm2-5-in-ova-sensitized-and-challenged-mice-and-the-expression-of-trpa1-and-trpv1-protein-in-lung
#19
Hong Liu, Xinsheng Fan, Naiqian Wang, Yuyan Zhang, Jinghua Yu
OBJECTIVE: To investigate the effects of PM2.5 on asthma-related phenotypes and on the expression of TRPA1, V1 protein in lung in a mouse model of asthma. METHODS: Female Balb/c mice were utilized to establish 28 and 42 day asthma models. Mice were sensitized with OVA and challenged with OVA, OVA plus normal saline (NS), or OVA plus PM2.5 at two doses, 1.6 mg·kg(-1) or 8.0 mg·kg(-1). PM2.5 was administrated by intratracheal instillationwithout anesthesia. 24 hours after the final OVA challenge changes in airway resistance (RI) and lung compliance (Cdyn) in response to acetylcholine chloride (ACH) were evaluated, and blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were taken...
January 19, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#20
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely impact human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of Vascular Endothelial Growth Factor (VEGF), a factor known to promote tumour growth...
January 17, 2017: Cancer Prevention Research
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