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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/28223230/myotoxicity-of-statins-mechanism-of-action
#2
REVIEW
Patrick du Souich, Ghislaine Roederer, Robert Dufour
Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations of statins in the myocyte and/or in presence of muscular conditions that may predispose to SIM. High concentrations of statins in the myocyte may occur whenever the activity of liver influx membrane transporters, namely OATP1B1, of drug metabolizing enzymes, and of liver and muscular efflux transporters, MDR1 and BCRP, is reduced...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28218274/trapping-of-ivermectin-by-a-pentameric-ligand-gated-ion-channel-upon-open-to-closed-isomerization
#3
Nurit Degani-Katzav, Moshe Klein, Moran Har-Even, Revital Gortler, Ruthi Tobi, Yoav Paas
Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. By activating invertebrate pentameric glutamate-gated chloride channels (GluCl receptors; GluClRs), IVM induces sustained chloride influx and long-lasting membrane hyperpolarization that inhibit neural excitation in nematodes. Although IVM activates the C. elegans heteromeric GluClα/β receptor, it cannot activate a homomeric receptor composed of the C. elegans GluClβ subunits...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217875/mechanisms-of-pruritogen-induced-activation-of-itch-nerves-in-isolated-mouse-skin
#4
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/28209107/gastro-intestinal-manifestations-in-cystic-fibrosis-patients
#5
REVIEW
S Van Biervliet, C de Clercq, D Declercq, E Van Braeckel, S Van Daele, F De Baets, D De Looze
Cystic fibrosis (CF) is a life-limiting disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). This defective chloride channel, present in different organ systems such as respiratory system, gastrointestinal tract, reproductive system and sweat glands, disturbs the ion and water transport over the membranes leading to the well known CF symptoms. CF has outgrown paediatric care, as half of CF patients are currently adults. The CF gastrointestinal tract has its own particularities...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28208271/cation-dependent-surface-charge-regulation-in-gated-nanofluidic-devices
#6
Marie Fuest, Kaushik K Rangharajan, Caitlin Boone, A T Conlisk, Shaurya Prakash
Surface charge governs nanoscale aqueous electrolyte transport, both in engineered analytical systems and in biological entities such as ion channels and ion pumps as a function of ion type and concentration. Embedded electrodes in a nanofluidic channel, isolated from the fluid in the channel by a dielectric layer, act as active, tunable gates to systematically modify local surface charge density at the interface between the nanochannel surface and the aqueous electrolyte solution, causing significant changes in measured nanochannel conductance...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#7
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28205343/association-of-chloride-intracellular-channel-4-and-indian-hedgehog-proteins-with-survival-of-patients-with-pancreatic-ductal-adenocarcinoma
#8
Qiong Zou, Zhulin Yang, Daiqiang Li, Ziru Liu, Yuan Yuan
Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question...
February 16, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28202726/two-tonoplast-mate-proteins-function-as-turgor-regulating-chloride-channels-in-arabidopsis
#9
Haiwen Zhang, Fu-Geng Zhao, Ren-Jie Tang, Yuexuan Yu, Jiali Song, Yuan Wang, Legong Li, Sheng Luan
The central vacuole in a plant cell occupies the majority of the cellular volume and plays a key role in turgor regulation. The vacuolar membrane (tonoplast) contains a large number of transporters that mediate fluxes of solutes and water, thereby adjusting cell turgor in response to developmental and environmental signals. We report that two tonoplast Detoxification efflux carrier (DTX)/Multidrug and Toxic Compound Extrusion (MATE) transporters, DTX33 and DTX35, function as chloride channels essential for turgor regulation in Arabidopsis Ectopic expression of each transporter in Nicotiana benthamiana mesophyll cells elicited a large voltage-dependent inward chloride current across the tonoplast, showing that DTX33 and DTX35 each constitute a functional channel...
February 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28198817/dynamic-properties-of-calcium-activated-chloride-currents-in-xenopus-laevis-oocytes
#10
Ildefonso M De la Fuente, Iker Malaina, Alberto Pérez-Samartín, María Dolores Boyano, Gorka Pérez-Yarza, Carlos Bringas, Álvaro Villarroel, María Fedetz, Rogelio Arellano, Jesus M Cortes, Luis Martínez
Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epithelial secretion and neuronal excitability. In addition, dysfunction of Cl(-) channels is involved in a variety of human diseases such as epilepsy, osteoporosis and different cancer types...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198360/secreted-clic3-drives-cancer-progression-through-its-glutathione-dependent-oxidoreductase-activity
#11
Juan R Hernandez-Fernaud, Elena Ruengeler, Andrea Casazza, Lisa J Neilson, Ellie Pulleine, Alice Santi, Shehab Ismail, Sergio Lilla, Sandeep Dhayade, Iain R MacPherson, Iain McNeish, Darren Ennis, Hala Ali, Fernanda G Kugeratski, Heba Al Khamici, Maartje van den Biggelaar, Peter V E van den Berghe, Catherine Cloix, Laura McDonald, David Millan, Aoisha Hoyle, Anna Kuchnio, Peter Carmeliet, Stella M Valenzuela, Karen Blyth, Huabing Yin, Massimiliano Mazzone, Jim C Norman, Sara Zanivan
The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2)...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28197715/vacuolar-ion-channels-in-the-liverwort-marchantia-polymorpha-influence-of-ion-channel-inhibitors
#12
Mateusz Koselski, Kazimierz Trebacz, Halina Dziubinska
Potassium-permeable slow activating vacuolar channels (SV) and chloride-permeable channels in the vacuole of the liverwort Marchantia polymorpha were characterized in respect to calcium dependence, selectivity, and pharmacology. The patch-clamp method was used in the study of ion channel activity in the vacuoles from the liverwort Marchantia polymorpha. The whole-vacuole recordings allowed simultaneous observation of two types of currents-predominant slow activated currents recorded at positive voltages and fast activated currents recorded at negative voltages...
February 14, 2017: Planta
https://www.readbyqxmd.com/read/28193731/selective-transport-of-neurotransmitters-and-modulators-by-distinct-volume-regulated-lrrc8-anion-channels
#13
Darius Lutter, Florian Ullrich, Jennifer C Lueck, Stefan Kempa, Thomas J Jentsch
In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine...
February 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28187828/molecular-characterization-and-expression-pattern-of-three-gaba-receptor-like-subunits-in-the-small-brown-planthopper-laodelphax-striatellus-hemiptera-delphacidae
#14
Qi Wei, Shun-Fan Wu, Cong-Fen Gao
Ionotropic γ-aminobutyric acid (GABA)-gated chloride channel receptors mediate rapid inhibitory neurotransmission in vertebrates and invertebrates. GABA receptors are well known to be the molecular targets of synthetic insecticides or parasiticides. Three GABA receptor-like subunits, LsLCCH3, LsGRD and LS8916, of the small brown planthopper, Laodelphax striatellus (Fallén), a major insect pest of crop systems in East Asia, had been identified and characterized in this study. All three genes were cloned using the reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE)...
March 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28177558/tmem16a-ano1-suppression-improves-response-to-antibody-mediated-targeted-therapy-of-egfr-and-her2-erbb2
#15
Sucheta Kulkarni, Anke Bill, Neal R Godse, Nayel I Khan, Jason I Kass, Kevin Steehler, Carolyn Kemp, Kara Davis, Carol A Bertrand, Avani R Vyas, Douglas E Holt, Jennifer R Grandis, L Alex Gaither, Umamaheswar Duvvuri
TMEM16A, a Ca(2+) -activated Cl(-) channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl(-) channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl(-) channel inhibition...
February 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28176803/three-novel-ano5-missense-mutations-in-caucasian-and-chinese-families-and-sporadic-cases-with-gnathodiaphyseal-dysplasia
#16
Lingling Jin, Yi Liu, Fanyue Sun, Michael T Collins, Keith Blackwell, Albert S Woo, Ernst J Reichenberger, Ying Hu
Gnathodiaphyseal dysplasia (GDD; MIM#166260) is an autosomal dominant syndrome with characteristic cemento-osseous lesions of jawbones, bone fragility, and diaphyseal sclerosis of tubular bones. To date, only five mutations in the proposed calcium-activated chloride channel ANO5/TMEM16E gene have been identified. In this study, we describe two families and two singular patients with three new mutations. One Caucasian family with seven affected members exhibited frequent bone fractures and florid osseous dysplasia (p...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28173798/spasmogenic-and-spasmolytic-activity-of-rind-of-punica-granatum-linn
#17
Niaz Ali, Ayesha Jamil, Syed Wadood Ali Shah, Ismail Shah, Ghayour Ahmed
BACKGROUND: Rind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range. METHODS: Rind of Punica granatum was subjected to shade drying...
February 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28164762/regulation-of-ion-channels-cellular-carriers-and-na-k-atpase-by-janus-kinase-3
#18
Mentor Sopjani, Shpëtim Thaçi, Berat Krasniqi, Miranda Selmonaj, Mark Rinnerthaler, Miribane Dërmaku-Sopjani
Janus kinase-3 (JAK3), a tyrosine kinase, is expressed in a variety of tissues, including the brain, and is involved in the signaling of cytokine receptors. JAK3 participates in numerous functions, among other the cell survival and proliferation, neuroprotection, apoptosis, as well as cellular response to hypoxia and ischemia-reperfusion. This kinase further contributes in the signaling of hematopoietic cell cytokine receptors, dendritic cells activation, maturation, and immune suppression as well as to cell volume regulation...
February 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28161542/vasorelaxation-effect-of-glycyrrhizae-uralensis-through-the-endothelium-dependent-pathway
#19
Chu Shan Tan, Yung Sing Ch'ng, Yean Chun Loh, Mohd Zaini Asmawi, Mariam Ahmad, Mun Fei Yam
ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza uralensis (G. uralensis) is one of the herbs used in traditional Chinese medicine (TCM) and serves as an envoy medicinal. Since G. uralensis plays a major role in the anti-hypertensive TCM formulae, we believe that G. uralensis might possess vasorelaxation activity. AIM OF THE STUDY: This study is designed to investigate the vasorelaxation effect of G. uralensis from various extracts and to study its pharmacology effect...
February 1, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28161538/chloride-channel-clc-2-enhances-intestinal-epithelial-tight-junction-barrier-function-via-regulation-of-caveolin-1-and-caveolar-trafficking-of-occludin
#20
Prashant K Nighot, Lana Leung, Thomas Y Ma
Previous studies have demonstrated that the chloride channel ClC-2 plays a critical role in intestinal epithelial tight junction (TJ) barrier function via intracellular trafficking of TJ protein occludin. To study the mechanism of ClC-2-mediated TJ barrier function and intracellular trafficking of occludin, we established ClC-2 over-expressing Caco-2 cell line (Caco-2(CLCN2)) by full length ClC-2 ORF transfection. ClC-2 over-expression (Caco-2(CLCN2)) significantly enhanced TJ barrier (increased TER by ≥2 times and reduced inulin flux by 50%) compared to control Caco-2(pEZ) cells...
February 2, 2017: Experimental Cell Research
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