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TRPA1 ion channel

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https://www.readbyqxmd.com/read/28620299/the-alkamide-trans-pellitorine-targets-ppar%C3%AE-via-trpv1-and-trpa1-to-reduce-lipid-accumulation-in-developing-3t3-l1-adipocytes
#1
Barbara Lieder, Mathias Zaunschirm, Ann-Katrin Holik, Jakob P Ley, Joachim Hans, Gerhard E Krammer, Veronika Somoza
Adipose tissue is an important endocrine organ in the human body. However, pathological overgrowth is associated with chronic illness. Regulation of adipogenesis and maturation of adipocytes via bioactive compounds in our daily diet has been in focus of research in the past years and showed promising results for agonists of the ion channels transient receptor potential channel (TRP) V1 and A1. Here, we investigated the anti-adipogenic potential and underlying mechanisms of the alkamide trans-pellitorine present in Piper nigrum via TRPV1 and TRPA1 in 3T3-L1 cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28571526/trpa1-channels-mediate-hgf-response-to-phenytoin
#2
M J López-González, E Luis, O Fajardo, V Meseguer, K Gers-Barlag, S Niñerola, F Viana
Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications-the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue...
March 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28530239/thermogenetic-neurostimulation-with-single-cell-resolution
#3
Yulia G Ermakova, Aleksandr A Lanin, Ilya V Fedotov, Matvey Roshchin, Ilya V Kelmanson, Dmitry Kulik, Yulia A Bogdanova, Arina G Shokhina, Dmitry S Bilan, Dmitry B Staroverov, Pavel M Balaban, Andrei B Fedotov, Dmitry A Sidorov-Biryukov, Evgeny S Nikitin, Aleksei M Zheltikov, Vsevolod V Belousov
Thermogenetics is a promising innovative neurostimulation technique, which enables robust activation of neurons using thermosensitive transient receptor potential (TRP) cation channels. Broader application of this approach in neuroscience is, however, hindered by a limited variety of suitable ion channels, and by low spatial and temporal resolution of neuronal activation when TRP channels are activated by ambient temperature variations or chemical agonists. Here, we demonstrate rapid, robust and reproducible repeated activation of snake TRPA1 channels heterologously expressed in non-neuronal cells, mouse neurons and zebrafish neurons in vivo by infrared (IR) laser radiation...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28526851/characterization-of-trpa-channels-in-the-starfish-patiria-pectinifera-involvement-of-thermally-activated-trpa1-in-thermotaxis-in-marine-planktonic-larvae
#4
Shigeru Saito, Gen Hamanaka, Narudo Kawai, Ryohei Furukawa, Jun Gojobori, Makoto Tominaga, Hiroyuki Kaneko, Yoko Satta
The vast majority of marine invertebrates spend their larval period as pelagic plankton and are exposed to various environmental cues. Here we investigated the thermotaxis behaviors of the bipinnaria larvae of the starfish, Patiria pectinifera, in association with TRPA ion channels that serve as thermal receptors in various animal species. Using a newly developed thermotaxis assay system, we observed that P. pectinifera larvae displayed positive thermotaxis toward high temperatures, including toward temperatures high enough to cause death...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28524111/synthesis-and-pharmacological-properties-of-novel-esters-based-on-monoterpenoids-and-glycine
#5
Mariia Nesterkina, Iryna Kravchenko
Esters based on mono- and bicyclic terpenoids with glycine have been synthesized via Steglich esterification and characterized by ¹H-NMR, IR, and mass spectral studies. Their analgesic and anti-inflammatory activities were investigated after transdermal delivery on models of formalin, capsaicin, and AITC-induced pain, respectively. Glycine esters of menthol and borneol exhibited higher antinociceptive action, whereas eugenol derivative significantly suppressed the development of the inflammatory process. The mechanism of competitive binding between terpenoid esters and TRPA1/TRPV1 agonists was proposed explaining significant analgesic effect of synthesized derivatives...
May 18, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28500286/a-kinase-anchoring-protein-79-150-scaffolds-transient-receptor-potential-a-1-phosphorylation-and-sensitization-by-metabotropic-glutamate-receptor-activation
#6
Allison Doyle Brackley, Ruben Gomez, Kristi A Guerrero, Armen N Akopian, Marc J Glucksman, Junhui Du, Susan M Carlton, Nathaniel A Jeske
Mechanical pain serves as a base clinical symptom for many of the world's most debilitating syndromes. Ion channels expressed by peripheral sensory neurons largely contribute to mechanical hypersensitivity. Transient Receptor Potential A 1 (TRPA1) is a ligand-gated ion channel that contributes to inflammatory mechanical hypersensitivity, yet little is known as to the post-translational mechanism behind its somatosensitization. Here, we utilize biochemical, electrophysiological, and behavioral measures to demonstrate that metabotropic glutamate receptor-induced sensitization of TRPA1 nociceptors stimulates targeted modification of the receptor...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498403/mus-musculus-microrna-449a-ameliorates-neuropathic-pain-by-decreasing-the-level-of-kcnma1-and-trpa1-and-increasing-the-level-of-tpte
#7
Shan Lu, Sichao Ma, Yunyun Wang, Tao Huang, Zhihua Zhu, Guoqing Zhao
Neuropathic pain is a nerve disorder characterized by the dysregulation of ion channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be associated with the molecular mechanisms underlying the altered levels of ion channels; however, the molecular mechanisms remain widely unknown. To investigate these mechanisms, the present study conducted a genomic analysis of miR between a unilateral spared nerve injury (SNI) model and sham control. Differentially expressed miRs between the SNI and sham groups were selected for transfection of DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently performed...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28480765/targeting-dorsal-root-ganglia-and-primary-sensory-neurons-for-the-treatment-of-chronic-pain
#8
Temugin Berta, Yawar Qadri, Ping-Heng Tan, Ru-Rong Ji
Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons...
May 16, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28478727/local-upregulation-of-transient-receptor-potential-ankyrin-1-and-transient-receptor-potential-vanilloid-1-ion-channels-in-rectosigmoid-deep-infiltrating-endometriosis
#9
Noémi Bohonyi, Krisztina Pohóczky, Bálint Szalontai, Anikó Perkecz, Krisztina Kovács, Béla Kajtár, Lajos Orbán, Tamás Varga, Sarolta Szegedi, József Bódis, Zsuzsanna Helyes, Miklós Koppán
Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis ( n = 15), uterine fibroid-induced moderate dysmenorrhoea ( n = 7) and tubal infertility with no pain ( n = 6)...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28399855/characterisation-of-a-murine-model-of-the-late-asthmatic-response
#10
Katie Baker, Kristof Raemdonck, Robert J Snelgrove, Maria G Belvisi, Mark A Birrell
BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the current available therapies are effective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In the search to understand disease pathogenesis and find effective therapies hypotheses are often tested in animal models before progressing into clinical studies. However, current dogma is that animal model data is often not predictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challenge induced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal model systems...
April 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#11
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28378773/polysulfides-h2sn-produced-from-the-interaction-of-hydrogen-sulfide-h2s-and-nitric-oxide-no-activate-trpa1-channels
#12
Ryo Miyamoto, Shin Koike, Yoko Takano, Norihiro Shibuya, Yuka Kimura, Kenjiro Hanaoka, Yasuteru Urano, Yuki Ogasawara, Hideo Kimura
Hydrogen sulfide (H2S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2S and NO generates polysulfides (H2Sn), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca(2+) and H2Sn, showed that H2Sn and their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377424/the-ca2-permeable-cation-trpv3-channel-an-emerging-pivotal-target-for-itch-and-skin-diseases
#13
Gongxin Wang, Kewei Wang
Temperature-sensitive transient receptor potential (thermo-TRP) channels such as TRPA1 and TRPV1 have been indicated as downstream ion channel targets in transduction of itch. As a member of thermos-TRPs, Ca2+-permeable nonselective cation TRPV3 channels are expressed abundantly in the skin keratinocytes. Recent identification of gain-of-function mutations of human TRPV3 from patients with Olmsted Syndrome characterized by severe itching and palmoplantar and periorificial keratoderma unveils its crucial role in chronic itch and skin diseases...
April 4, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28332600/calmodulin-is-responsible-for-ca-2-dependent-regulation-of-trpa1-channels
#14
Raquibul Hasan, Alasdair T S Leeson-Payne, Jonathan H Jaggar, Xuming Zhang
TRPA1 is a Ca(2+)-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca(2+), with low Ca(2+) potentiating and high Ca(2+) inactivating TRPA1. However, it remains unknown how Ca(2+) exerts such contrasting effects. Here, we show that Ca(2+) regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca(2+)-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca(2+)-evoked potentiation of TRPA1 at low Ca(2+), but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca(2+)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#15
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Ying Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters, but understanding of these channels remains inadequate. Here we focus on transient receptor potential canonical 4 and 5 proteins (TRPC4 and TRPC5), which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested, including in epilepsy, innate fear, pain, and cardiac remodeling, but limitations in tools to probe these channels have restricted progress...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28320952/identification-of-a-putative-binding-site-critical-for-general-anesthetic-activation-of-trpa1
#16
Hoai T Ton, Thieu X Phan, Ara M Abramyan, Lei Shi, Gerard P Ahern
General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABAA receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28293191/an-exploration-of-charge-compensating-ion-channels-across-the-phagocytic-vacuole-of-neutrophils
#17
Juliet R Foote, Philippe Behe, Mathew Frampton, Adam P Levine, Anthony W Segal
Neutrophils phagocytosing bacteria and fungi exhibit a burst of non-mitochondrial respiration that is required to kill and digest the engulfed microbes. This respiration is accomplished by the movement of electrons across the wall of the phagocytic vacuole by the neutrophil NADPH oxidase, NOX2. In this study, we have attempted to identify the non-proton ion channels or transporters involved in charge compensation by examining the effect of inhibitors on vacuolar pH and cross-sectional area, and on oxygen consumption...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28277613/activation-of-mutated-trpa1-ion-channel-by-resveratrol-in-human-prostate-cancer-associated-fibroblasts-caf
#18
Eric Vancauwenberghe, Lucile Noyer, Sandra Derouiche, Loïc Lemonnier, Pierre Gosset, Laura R Sadofsky, Pascal Mariot, Marine Warnier, Alexandre Bokhobza, Christian Slomianny, Brigitte Mauroy, Jean-Louis Bonnal, Etienne Dewailly, Philippe Delcourt, Laurent Allart, Emilie Desruelles, Natalia Prevarskaya, Morad Roudbaraki
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells, and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28239353/transient-receptor-potential-ankyrin-1-channel-expression-on-peripheral-blood-leukocytes-from-rheumatoid-arthritic-patients-and-correlation-with-pain-and-disability
#19
Ione Pereira, Saulo J F Mendes, Domingos M S Pereira, Thayanne F Muniz, Valderlane L P Colares, Cinara R A V Monteiro, Mahiba M R de S Martins, Marcos A G Grisotto, Valério Monteiro-Neto, Sílvio G Monteiro, João B Calixto, Susan D Brain, Elizabeth S Fernandes
Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA)...
2017: Frontiers in Pharmacology
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
#20
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...
March 22, 2017: Journal of Ethnopharmacology
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