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Transient receptor potential receptor

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https://www.readbyqxmd.com/read/28092830/trpv1-antagonism-by-piperazinyl-aryl-compounds-a-topomer-comfa-study-and-its-use-in-virtual-screening-for-identification-of-novel-antagonists
#1
Rajendra Kristam, Shashidhar N Rao, Anne Sudha D'Cruz, Vijayalakshmi Mahadevan, Vellarkad N Viswanadhan
Transient Receptor Potential Vanilloid, member 1 (TRPV1), is a non-selective cation channel belonging to the transient receptor potential (TRP) family of ion channels. It occurs in the peripheral and central nervous system, activated by a variety of exogenous and endogenous stimuli, thus playing a key role in transmission of pain. This has been a target for chronic pain since more than a decade and a number of antagonists that progressed into clinical trials have failed due to the unexpected side effect of core body temperature rise, thus halting progress in this field...
January 7, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28090285/pulmonary-vascular-and-ventricular-dysfunction-in-the-susceptible-patient-2015-grover-conference-series
#2
REVIEW
Bradley A Maron, Roberto F Machado, Larissa Shimoda
Pulmonary blood vessel structure and tone are maintained by a complex interplay between endogenous vasoactive factors and oxygen-sensing intermediaries. Under physiological conditions, these signaling networks function as an adaptive interface between the pulmonary circulation and environmental or acquired perturbations to preserve oxygenation and maintain systemic delivery of oxygen-rich hemoglobin. Chronic exposure to hypoxia, however, triggers a range of pathogenetic mechanisms that include hypoxia-inducible factor 1α (HIF-1α)-dependent upregulation of the vasoconstrictor peptide endothelin 1 in pulmonary endothelial cells...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089266/trpc1-orai1-and-stim1-in-soce-friends-in-tight-spaces
#3
REVIEW
Indu S Ambudkar, Lorena Brito de Souza, Hwei Ling Ong
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in miscellaneous cell types. The transient receptor potential canonical 1 (TRPC1) is the first member of the TRPC channel subfamily to be identified as a molecular component of SOCE. While TRPC1 has been shown to contribute to SOCE and regulate various functions in many cells, none of the reported TRPC1-mediated currents resembled ICRAC, the highly Ca(2+)-selective store-dependent current first identified in lymphocytes and mast cells...
December 30, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28088386/trypsin-induces-biphasic-muscle-contraction-and-relaxation-via-transient-receptor-potential-vanilloid-1-and-neurokinin-receptors-1-2-in-porcine-esophageal-body
#4
Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura
Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28087925/host-responses-to-urinary-tract-infections-and-emerging-therapeutics-sensation-and-pain-within-the-urinary-tract
#5
Lori A Birder, David J Klumpp
Urinary tract infection (UTI) pathogenesis is understood increasingly at the level of the uropathogens and the cellular and molecular mediators of host inflammatory responses. However, little is known about the mediators of symptoms during UTI and what distinguishes symptomatic events from asymptomatic bacteriuria. Here, we review bladder physiology and sensory pathways in the context of an emerging literature from murine models dissecting the host and pathogen factors mediating pain responses during UTI. The bladder urothelium is considered a mediator of sensory responses and appears to play a role in UTI pain responses...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087653/identification-of-regulatory-networks-and-hub-genes-controlling-soybean-seed-set-and-size-using-rna-sequencing-analysis
#6
Juan Du, Shoudong Wang, Cunman He, Bin Zhou, Yong-Ling Ruan, Huixia Shou
To understand the gene expression networks controlling soybean seed set and size, transcriptome analyses were performed in three early seed developmental stages, using two genotypes with contrasting seed size. The two-dimensional data set provides a comprehensive and systems-level view on dynamic gene expression networks underpinning soybean seed set and subsequent development. Using pairwise comparisons and weighted gene coexpression network analyses, we identified modules of coexpressed genes and hub genes for each module...
January 13, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28081185/upregulated-expression-of-transient-receptor-potential-cation-channel-subfamily-v-receptors-in-mucosae-of-patients-with-oral-squamous-cell-carcinoma-and-patients-with-a-history-of-alcohol-consumption-or-smoking
#7
Akiko Sakakibara, Shunsuke Sakakibara, Junya Kusumoto, Daisuke Takeda, Takumi Hasegawa, Masaya Akashi, Tsutomu Minamikawa, Kazunobu Hashikawa, Hiroto Terashi, Takahide Komori
OBJECTIVES: Transient receptor potential cation channel (subfamily V, members 1-4) (TRPV1-4) are expressed in skin and neurons and activated by external stimuli in normal mucosae of all oral cavity sites. The oral cavity is exposed to various stimuli, including temperature, mechanical stimuli, chemical substances, and changes in pH, and, notably, the risk factors for oncogenic transformation in oral squamous epithelium are the same as the external stimuli received by TRPV1-4 receptors...
2017: PloS One
https://www.readbyqxmd.com/read/28078622/evidence-that-polycystins-are-involved-in-hydra-cnidocyte-discharge
#8
Susan McLaughlin
Like other cnidarians, the freshwater organism Hydra is characterized by the possession of cnidocytes (stinging cells). Most cnidocytes are located on hydra tentacles, where they are organized along with sensory cells and ganglion cells into battery complexes. The function of the battery complexes is to integrate multiple types of stimuli for the regulation of cnidocyte discharge. The molecular mechanisms controlling the discharge of cnidocytes are not yet fully understood, but it is known that discharge depends on extracellular Ca(2+) and that mechanically induced cnidocyte discharge can be enhanced by the presence of prey extracts and other chemicals...
March 2017: Invertebrate Neuroscience: IN
https://www.readbyqxmd.com/read/28077580/peptide-from-sea-anemone-metridium-senile-affects-transient-receptor-potential-ankyrin-repeat-1-trpa1-function-and-produces-analgesic-effect
#9
Yulia A Logashina, Irina V Mosharova, Yulia V Korolkova, Irina V Shelukhina, Igor A Dyachenko, Victor A Palikov, Yulia A Palikova, Arkadii N Murashev, Sergey A Kozlov, Klara Stensvåg, Yaroslav A Andreev
The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate (AITC)- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is a 35-amino-acid peptide cross-linked by two disulfide bridges, named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28077439/the-functional-expression-of-transient-receptor-potential-channels-in-the-mouse-endometrium
#10
Katrien De Clercq, Charlotte Van den Eynde, Aurélie Hennes, Rieta Van Bree, Thomas Voets, Joris Vriens
STUDY QUESTION: Does mouse endometrial epithelial cells and stromal cells have a similar transient receptor potential (TRP)-channel expression profile and to that found in the human endometrium? SUMMARY ANSWER: Mouse endometrial epithelial and stromal cells have a distinct TRP channel expression profile analogous to what has been found in human endometrium, and hence suggests the mouse a good model to investigate the role of TRP channels in reproduction. WHAT IS KNOWN ALREADY: An optimal intercellular communication between epithelial and stromal endometrial cells is crucial for successful reproduction...
January 6, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28076819/full-spectral-multiplexing-of-bioluminescence-resonance-energy-transfer-in-three-trpv-channels
#11
Hermanus Johannes Ruigrok, Guillaume Shahid, Bertrand Goudeau, Florence Poulletier de Gannes, Emmanuelle Poque-Haro, Annabelle Hurtier, Isabelle Lagroye, Pierre Vacher, Stéphane Arbault, Neso Sojic, Bernard Veyret, Yann Percherancier
Multiplexed bioluminescence resonance energy transfer (BRET) assays were developed to monitor the activation of several functional transient receptor potential (TRP) channels in live cells and in real time. We probed both TRPV1 intramolecular rearrangements and its interaction with Calmodulin (CaM) under activation by chemical agonists and temperature. Our BRET study also confirmed that: (1) capsaicin and heat promoted distinct transitions, independently coupled to channel gating, and that (2) TRPV1 and Ca(2+)-bound CaM but not Ca(2+)-free CaM were preassociated in resting live cells, while capsaicin activation induced both the formation of more TRPV1/CaM complexes and conformational changes...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28073836/ionotropic-glutamate-receptors-activate-cell-signaling-in-response-to-glutamate-in-schwann-cells
#12
Wendy M Campana, Elisabetta Mantuano, Pardis Azmoon, Kenneth Henry, Michael A Banki, John H Kim, Donald P Pizzo, Steven L Gonias
In the peripheral nervous system, Schwann cells (SCs) demonstrate surveillance activity, detecting injury and undergoing trans-differentiation to support repair. SC receptors that detect peripheral nervous system injury remain incompletely understood. We used RT-PCR to profile ionotropic glutamate receptor expression in cultured SCs. We identified subunits required for assembly of N-methyl-d-aspartic acid (NMDA) receptors (NMDA-R), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and kainate receptors...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28073835/mechanosensitive-transient-receptor-potential-vanilloid-4-regulates-dermatophagoides-farinae-induced-airway-remodeling-via-2-distinct-pathways-modulating-matrix-synthesis-and-degradation
#13
Farai Gombedza, Vinay Kondeti, Nosayba Al-Azzam, Stephanie Koppes, Ernest Duah, Prachi Patil, Madison Hexter, Daniel Phillips, Charles K Thodeti, Sailaja Paruchuri
Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4 knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4 knockout mice showed diminished differentiation potential compared with wild-type mice...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28066924/side-chain-flexibility-and-coupling-between-the-s4-s5-linker-and-the-trp-domain-in-thermo-sensitive-trp-channels-insights-from-protein-modeling
#14
Sergio Romero-Romero, Froylan Gómez-Lagunas, Daniel Balleza
The transient receptor potential (TRP) superfamily is subdivided into several subfamilies on the basis of sequence similarity, which is highly heterogeneous but shows a molecular architecture that resembles the one present in members of the Kv channel superfamily. Because of this diversity, they produce a large variety of channels with different gating and permeability properties. Elucidation of these particular features necessarily requires comparative studies based on structural and functional data. The present study aims to compilate, analyze, and determine, in a coherent way, the relationship between intrinsic side-chain flexibility and the allosteric coupling in members of the TRPV, TRPM, and TRPC families...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28066150/calcium-permeability-of-transient-receptor-potential-canonical-trpc-4-channels-measured-by-trpc4-gcamp6s
#15
Juyeon Ko, Jongyun Myeong, Dongki Yang, Insuk So
Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. A TRPC4 specific activator, (-)-englerin A, induced both current and calcium fluorescence with the similar time course...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28063212/regulation-of-chondrocyte-functions-by-transient-receptor-potential-cation-channel-v6-in-osteoarthritis
#16
Tengfei Song, Jun Ma, Lei Guo, Peng Yang, Xuhui Zhou, Tianwen Ye
Transient receptor potential vanilloid (TRPV) channels function to maintain the dynamic balance of calcium signaling and calcium metabolism in bones. The goal of this study was to determine the potential role of TRPV6 in regulation of chondrocytes. The level of TRPV6 expression was analyzed by western blot in articular cartilage derived from the knee joints of osteoarthritis (OA) rat models and OA patients. Bone structure and osteoarthritic changes in the knee joints of TRPV6 knockout mice were examined using micro-computed and histological analysis at the age of 6 and 12 months old...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28062998/high-glucose-enhances-isoflurane-induced-neurotoxicity-by-regulating-trpc-dependent-calcium-influx
#17
ZhongJie Liu, ChangQing Ma, Wei Zhao, QingGuo Zhang, Rui Xu, HongFei Zhang, HongYi Lei, ShiYuan Xu
Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca(2+)). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca(2+) influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca(2+) influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure...
January 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28062485/activation-of-bitter-taste-receptors-in-pulmonary-nociceptors-sensitizes-trpv1-channels-through-plc-and-pkc-signaling-pathway
#18
Qihai Gu, Deanna S Joe, Carolyn A Gilbert
Bitter taste receptors (T2Rs), a G-protein-coupled receptor family capable of detecting numerous bitter-tasting compounds, have recently been shown to be expressed and play diverse roles in many extraoral tissues. Here we report the functional expression of T2Rs in rat pulmonary sensory neurons. In anesthetized spontaneously breathing rats, intratracheal instillation of T2Rs agonist chloroquine (10 mM, 0.1 ml) significantly augmented chemoreflexes evoked by right-atrial injection of capsaicin, a specific activator for transient receptor potential vanilloid receptor 1 (TRPV1); whereas intravenous infusion of chloroquine failed to significantly affect capsaicin-evoked reflexes...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28060940/clock-genes-regulate-the-circadian-expression-of-piezo1-trpv4-connexin26-and-vnut-in-an-ex-vivo-mouse-bladder-mucosa
#19
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Karl-Erik Andersson, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
OBJECTIVES: ClockΔ19/Δ19 mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from ClockΔ19/Δ19 mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular nucleotide transporter (VNUT) and Connexin26(Cx26), in addition to clock genes. MATERIALS AND METHODS: Eight- to twelve-week-old male C57BL/6 mice (WT) and age- and sex-matched C57BL/6 ClockΔ19/Δ19 mice, which were bred under 12-h light/dark conditions for 2 weeks, were used...
2017: PloS One
https://www.readbyqxmd.com/read/28059868/a-novel-inhibitor-of-active-protein-kinase-g-attenuates-chronic-inflammatory-and-osteoarthritic-pain
#20
Ying-Ju Sung, Nelson Sofoluke, Mary Nkamany, Shixian Deng, Yuli Xie, Jeremy Greenwood, Ramy Farid, Donald W Landry, Richard T Ambron
Activating Protein kinase-1α (PKG-1α) induces a long-term hyperexcitability (LTH) in nociceptive neurons. Since the LTH correlates directly with chronic pain in many animal models we tested the hypothesis that inhibiting PKG-1α would attenuate LTH-mediated pain. We first synthesized and characterized compound N46 (propoxybenzoyl)benzamidopyrrolidin-3-yl)-1H-indazole-5-carboxamide). N46 inhibits PKG-1α with an IC50 of 7.5nmol, was highly selective when tested against a panel of 274 kinases, and tissue distribution studies indicate that it does not enter the CNS...
December 30, 2016: Pain
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