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chloride channel activators

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https://www.readbyqxmd.com/read/29785630/calcium-channels-rho-kinase-protein-kinase-c-and-phospholipase-c-pathways-mediate-mercury-chloride-induced-myometrial-contractions-in-rats
#1
Swati Koli, Atul Prakash, Soumen Choudhury, Rajesh Mandil, Satish K Garg
Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl2 )-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl2 was recorded using data acquisition system-based physiograph. HgCl2 produced concentration-dependent (10 nM-100 μM) uterotonic effect which was significantly (p < 0...
May 21, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29780533/a-halogen-bond-mediated-highly-active-artificial-chloride-channel-with-high-anticancer-activity
#2
Changliang Ren, Xin Ding, Arundhati Roy, Jie Shen, Shaoyuan Zhou, Feng Chen, Sam Fong Yau Li, Haisheng Ren, Yi Yan Yang, Huaqiang Zeng
Chloride-selective transmembrane carriers or channels might have possible uses in treating channelopathies or cancers. While chloride carriers have been extensively investigated, the corresponding chloride channels have remained limitedly studied. Moreover, all hitherto reported channel systems lack clearly definable and readily modifiable positions in their structures for the reliable construction and combinatorial optimization of their ion transport properties. As a result, the existing channels are limited by their large molecular weight, weak activity or low anion selectivity...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29772528/peptide-inhibitors-of-chloride-channels-for-treating-secretory-diarrhea
#3
Jitu Ma, Xueqin Ding, Yulong Yin, Pengfei Huang
Morbidity and mortality associated with diarrheal diseases remain significant burdens on global health. In the developing world, the major sources of secretory diarrhea are infectious, including those caused by bacteria such as enterotoxic Escherichia coli , and viruses such as rotavirus. In many cases of secretory diarrhea, activation of pathways for cyclic nucleotides and/or Ca2+ signaling in the apical membrane of enterocytes increases the conductance of Cl- channels at the enterocyte lumen-facing membrane...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29758025/clca2-is-a-positive-regulator-of-store-operated-calcium-entry-and-tmem16a
#4
Aarushi Sharma, Grace Ramena, Yufang Yin, Louis Premkumar, Randolph C Elble
The Chloride Channel Accessory (CLCA) protein family was first characterized as regulators of calcium-activated chloride channel (CaCC) currents (ICaCC), but the mechanism has not been fully established. We hypothesized that CLCAs might regulate ICaCC by modulating intracellular calcium levels. In cells stably expressing human CLCA2 or vector, we found by calcium imaging that CLCA2 moderately enhanced intracellular-store release but dramatically increased store-operated entry of calcium upon cytosolic depletion...
2018: PloS One
https://www.readbyqxmd.com/read/29750923/ion-channel-modulators-in-cystic-fibrosis
#5
REVIEW
Martina Gentzsch, Marcus A Mall
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains one of the most common life-shortening genetic diseases affecting the lung and other organs. CFTR functions as a cAMP-dependent anion channel that transports chloride and bicarbonate across epithelial surfaces and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacological modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach...
May 8, 2018: Chest
https://www.readbyqxmd.com/read/29748816/epicatechin-s-cardiovascular-protective-effects-are-mediated-via-opioid-receptors-and-nitric-oxide
#6
Kirsty MacRae, Kylie Connolly, Rebecca Vella, Andrew Fenning
PURPOSE: Cardiovascular disease is the leading cause of mortality globally. Epicatechin has previously been shown to improve vascular responses and possess cardioprotective properties. However, the mechanisms underpinning these cardiotropic outcomes remain unknown. The aim of this study was to further identify epicatechin's mechanism of action in the cardiovasculature. METHODS: The effects of epicatechin on isolated rat conduit arteries, resistance vessels and cardiac electrophysiology were investigated on resting tension and precontracted vessels and cardiac action potential parameters, both in the presence and in the absence of various antagonists...
May 10, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29748496/calcium-activated-cl-channel-insights-on-the-molecular-identity-in-epithelial-tissues
#7
REVIEW
Trey S Rottgen, Andrew J Nickerson, Vazhaikkurichi M Rajendran
Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca2+ -activated Cl&minus; secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca2+ -activated Cl&minus; channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca2+ -sensitivity of the channel...
May 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29743348/humidity-regulated-clca2-protects-the-epidermis-from-hyperosmotic-stress
#8
Kristin Seltmann, Michael Meyer, Jitka Sulcova, Tobias Kockmann, Ulrike Wehkamp, Stephan Weidinger, Ulrich Auf dem Keller, Sabine Werner
Low environmental humidity aggravates symptoms of the inflammatory skin disease atopic dermatitis (AD). Using mice that develop AD-like signs, we show that an increase in environmental humidity rescues their cutaneous inflammation and associated epidermal abnormalities. Quantitative proteomics analysis of epidermal lysates of mice kept at low or high humidity identified humidity-regulated proteins, including chloride channel accessory 3A2 (CLCA3A2), a protein with previously unknown function in the skin. The epidermis of patients with AD, organotypic skin cultures under dry conditions, and cultured keratinocytes exposed to hyperosmotic stress showed up-regulation of the nonorthologous human homolog CLCA2...
May 9, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29738885/regulation-of-seizure-induced-mecp2-ser421-phosphorylation-in-the-developing-brain
#9
Evan C Rosenberg, Jocelyn J Lippman-Bell, Marcus Handy, Samantha S Soldan, Sanjay Rakhade, Cristina Hilario-Gomez, Kaitlyn Folweiler, Leah Jacobs, Frances E Jensen
Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of CaV 1.2 L-type voltage gated calcium (Ca2+ ) channels (LT-VGCCs) and Ca2+ -permeable AMPARs (CP-AMPARs) lacking GluA2 subunits. We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca2+ -dependent signaling pathways including that of methyl-CPG-binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome...
May 5, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29723292/caenorhabditis-elegans-susceptibility-to-daldinia-cf-concentrica-bioactive-volatiles-is-coupled-with-expression-activation-of-the-stress-response-transcription-factor-daf-16-a-part-of-distinct-nematicidal-action
#10
Payal Sanadhya, Patricia Bucki, Orna Liarzi, David Ezra, Abraham Gamliel, Sigal Braun Miyara
The bionematicidal effect of a synthetic volatile mixture (SVM) of four volatile organic compounds (VOCs) emitted by the endophytic fungus Daldinia cf. concentrica against the devastating plant-parasitic root-knot nematode Meloidogyne javanica has been recently demonstrated in both in vitro and greenhouse experiments. However, the mode of action governing the observed irreversible paralysis of J2 larvae upon exposure to SVM is unknown. To unravel the mechanism underlying the anthelmintic and nematicidal activities, we used the tractable model worm Caenorhabditis elegans...
2018: PloS One
https://www.readbyqxmd.com/read/29719171/pannexin1-a-multi-function-and-multi-conductance-permeability-membrane-channel
#11
Junjie Wang, Gerhard Dahl
Of the three pannexins in vertebrate proteomes, pannexin1 (Panx1) is the only one well characterized, and it is generally accepted that Panx1 functions as an ATP release channel for signaling to other cells. However, the ATP permeability of the channel is only observed with certain stimuli, including low oxygen, mechanical stress and elevated extracellular potassium ion concentration. Otherwise, the Panx1 channel is selective for chloride ions and exhibits no ATP permeability when stimulated simply by depolarization to positive potentials...
May 2, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29719168/cationic-control-of-panx1-channel-function
#12
Junjie Wang, David George Jackson, Gerhard Dahl
The sequence and predicted membrane topology of Pannexin1 (Panx1) places it in the family of gap junction proteins. However, rather than forming gap junction channels, Panx1 forms channels in the non-junctional membrane. Panx1 operates in two distinct open states, depending on the mode of stimulation. The exclusively voltage-gated channel has a small conductance (<100 pS) and is highly selective for the flux of chloride ions. The Panx1 channel activated by various physiological stimuli or by increased concentrations of extracellular potassium ions has a large conductance (~500 pS, however with multiple, long lasting subconductance states) and is non-selectively permeable to small molecules, including ATP...
May 2, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29713521/new-experimental-models-of-retinal-degeneration-for-screening-molecular-photochromic-ion-channel-blockers
#13
A Yu Rotov, L A Astakhova, V S Sitnikova, A A Evdokimov, V M Boitsov, M V Dubina, M N Ryazantsev, M L Firsov
Application of molecular photochromic ion channel blockers to recover the visual function of a degenerated retina is one of the promising trends in photopharmacology. To this day, several photochromic azobenzene-based compounds have been proposed and their functionality has been demonstrated on cell lines and knockout mouse models. Further advance necessitates testing of the physiological activity of a great number of new compounds. The goal of this study is to propose animal models of photoreceptor degeneration that are easier to obtain than knockout mouse models but include the main features required for testing the physiological activity of molecular photoswitches...
January 2018: Acta Naturae
https://www.readbyqxmd.com/read/29704811/involvement-of-ion-channels-in-allergy
#14
REVIEW
Lucette Pelletier, Magali Savignac
Allergic asthma is a complex disease, often characterized by an inappropriate Th2 response to normally harmless allergens. Epithelial cells damaged or activated by the allergen produce IL-33, TSLP and IL-25, activating ILC2 and dendritic cells. The latter migrate into lymph nodes where they induce Th2-cell commitment. Th2 and other type 2 innate inflammatory cells trigger inflammation and airway hyper-reactivity. The toolbox consisting of the ion channels varies from one cellular type to another and depends on its activation state, offering the possibility to design novel drugs in the field of allergy...
April 25, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29704483/the-potent-insulin-secretagogue-effect-of-betulinic-acid-is-mediated-by-potassium-and-chloride-channels
#15
Allisson Jhonatan Gomes Castro, Luisa Helena Cazarolli, Lizandra C Bretanha, Paola Miranda Sulis, Diana Patricia Rey Padilla, Diana Marcela Aragón Novoa, Betina Fernanda Dambrós, Moacir G Pizzolatti, Fátima Regina Mena Barreto Silva
Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium...
April 25, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29701819/genome-wide-association-study-for-bone-strength-in-laying-hens
#16
B Raymond, A M Johansson, H A McCormack, R H Fleming, M Schmutz, I C Dunn, D J De Koning
Bone fracture in egg laying hens is a growing welfare and economic concern in the industry. Although environmental conditions and management (especially nutrition) can exacerbate it, the primary cause of bone weakness and the resulting fractures is believed to have a genetic basis. To test this hypothesis, we performed a genome-wide association study to identify the loci associated with bone strength in laying hens. Genotype and phenotype data were obtained from 752 laying hens belonging to the same pure line population...
April 26, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29686743/antinociceptive-activity-of-methanolic-extract-of-clinacanthus-nutans-leaves-possible-mechanisms-of-action-involved
#17
Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Rushduddin Al Jufri Roosli, Mohd Hijaz Mohd Sani, Maizatul Hasyima Omar, Siti Farah Mohd Tohid, Fezah Othman, Siew Mooi Ching, Arifah Abdul Kadir
Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes ( β -funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α 2 -noradrenergic (yohimbine), β -adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride)...
2018: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/29675710/salt-water-and-skin-interactions-new-lines-of-evidence
#18
REVIEW
Jose Manuel Carbajo, Francisco Maraver
In Health Resort Medicine, both balneotherapy and thalassotherapy, salt waters and their peloids, or mud products are mainly used to treat rheumatic and skin disorders. These therapeutic agents act jointly via numerous mechanical, thermal, and chemical mechanisms. In this review, we examine a new mechanism of action specific to saline waters. When topically administered, this water rich in sodium and chloride penetrates the skin where it is able to modify cellular osmotic pressure and stimulate nerve receptors in the skin via cell membrane ion channels known as "Piezo" proteins...
April 19, 2018: International Journal of Biometeorology
https://www.readbyqxmd.com/read/29674316/activation-of-renal-clc-k-chloride-channels-depends-on-an-intact-n-terminus-of-their-accessory-subunit-barttin
#19
Daniel Wojciechowski, Stefan Thiemann, Christina Schaal, Alina Rahtz, Jeanne de la Roche, Birgit Begemann, Toni Becher, Martin Fischer
ClC-K channels belong to the CLC family of chloride channels and chloride/proton antiporters. They contribute to sodium chloride reabsorption in Henle's loop of the kidney and to potassium secretion into the endolymph by the stria vascularis of the inner ear. Their accessory subunit barttin stabilizes the ClC-K/barttin complex, promotes its insertion into the surface membrane, and turns the pore-forming subunits into a conductive state. Barttin mutations cause Bartter syndrome type IV, a salt wasting nephropathy with sensorineural deafness...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29669921/a-selective-class-of-inhibitors-for-the-clc-ka-chloride-ion-channel
#20
Anna K Koster, Chase A P Wood, Rhiannon Thomas-Tran, Tanmay S Chavan, Jonas Almqvist, Kee-Hyun Choi, J Du Bois, Merritt Maduke
CLC proteins are a ubiquitously expressed family of chloride-selective ion channels and transporters. A dearth of pharmacological tools for modulating CLC gating and ion conduction limits investigations aimed at understanding CLC structure/function and physiology. Herein, we describe the design, synthesis, and evaluation of a collection of N -arylated benzimidazole derivatives (BIMs), one of which (BIM1) shows unparalleled (>20-fold) selectivity for CLC-Ka over CLC-Kb, the two most closely related human CLC homologs...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
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