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Acid-sensing ion channels

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https://www.readbyqxmd.com/read/28303465/pharmacotherapy-in-generalized-anxiety-disorder-novel-experimental-medicine-models-and-emerging-drug-targets
#1
REVIEW
David S Baldwin, Ruihua Hou, Robert Gordon, Nathan T M Huneke, Matthew Garner
Many pharmacological and psychological approaches have been found efficacious in patients with generalized anxiety disorder (GAD), but many treatment-seeking patients will not respond and others will relapse despite continuing with interventions that initially had beneficial effects. Other patients will respond but then stop treatment early because of untoward effects such as sexual dysfunction, drowsiness, and weight gain. There is much scope for the development of novel approaches that could have greater overall effectiveness or acceptability than currently available interventions or that have particular effectiveness in specific clinical subgroups...
March 16, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28300265/catalytic-routes-to-fuels-from-c1-and-oxygenate-molecules
#2
Shuai Wang, Iker Agirrezabal-Telleria, Aditya Bhan, Dante Simonetti, Kazuhiro Takanabe, Enrique Iglesia
This account illustrates concepts in chemical kinetics underpinned by the formalism of transition state theory using catalytic processes that enable the synthesis of molecules suitable as fuels from C1 and oxygenate reactants. Such feedstocks provide an essential bridge towards a carbon-free energy future, but their volatility and low energy density require the formation of new C-C bonds and the removal of oxygen. These transformations are described here through recent advances in our understanding of the mechanisms and site requirements in catalysis by surfaces, with emphasis on enabling concepts that tackle ubiquitous reactivity and selectivity challenges...
March 16, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/28298159/biological-behavior-of-human-nucleus-pulposus-mesenchymal-stem-cells-in-response-to-changes-in-the-acidic-environment-during-intervertebral-disc-degeneration
#3
Jianjun Liu, Hui Tao, Cailiang Shen, Xiaoying Liu, Hanbang Wang, Fulong Dong, Renjie Zhang, Jie Li, Peng Ge, Peiwen Song, Huaqing Zhang, Peng Xu
An acidic environment is vital for the maintenance of cellular activities but can be affected tremendously during intervertebral disc degeneration. The effect of changes in the acidity of the environment on human nucleus pulposus mesenchymal stem cells (NP-MSCs) is unknown, however. Thus, this study aimed to observe the biological effects of acidic conditions mimicking a degenerated intervertebral disc on NP-MSCs in vitro. NP-MSCs were isolated from patients with lumbar disc herniation and were further identified by their immunophenotypes and multilineage differentiation...
March 16, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28294983/on-the-emerging-role-of-the-taste-receptor-type-1-t1r-family-of-nutrient-sensors-in-the-musculoskeletal-system
#4
REVIEW
Shoichiro Kokabu, Jonathan W Lowery, Takashi Toyono, Tsuyoshi Sato, Tetsuya Yoda
The special sense of taste guides and guards food intake and is essential for body maintenance. Salty and sour tastes are sensed via ion channels or gated ion channels while G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family sense sweet and umami tastes and GPCRs of the taste receptor type 2 (T2R) family sense bitter tastes. T1R and T2R receptors share similar downstream signaling pathways that result in the stimulation of phospholipase-C-β2. The T1R family includes three members that form heterodimeric complexes to recognize either amino acids or sweet molecules such as glucose...
March 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28283476/alveolar-non-selective-channels-are-asic1a-%C3%AE-enac-channels-and-contribute-to-afc
#5
Phi T Trac, Tiffany L Thai, Valerie Linck, Li Zou, Megan M Greenlee, Qiang Yue, Otor K Al-Khalili, Abdel A Alli, Amity F Eaton, Douglas C Eaton
A thin fluid layer in alveoli is normal and results from a balance of fluid entry and fluid uptake by transepithelial salt and water reabsorption. Conventional wisdom suggests the reabsorption is via epithelial Na(+) channels (ENaC), but if all Na(+) reabsorption was via ENaC, then amiloride, an ENaC inhibitor, should block AFC. But amiloride blocks only half of AFC. The reason for failure to block is clear from single channel measurements from alveolar epithelial cells: ENaC channels are observed, but another channel is present at the same frequency that is non-selective for Na(+) over K(+), has a larger conductance, and shorter open and closed times...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28265090/deactivation-kinetics-of-acid-sensing-ion-channel-1a-are-strongly-ph-sensitive
#6
David M MacLean, Vasanthi Jayaraman
Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that accompanies neurotransmission. In response to such brief acidic transients, both recombinant and native ASICs show extremely rapid deactivation in outside-out patches when jumping from a pH 5 stimulus to a single resting pH of 8...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263552/polyelectrolyte-layer-by-layer-assembly-on-organic-electrochemical-transistors
#7
Anna-Maria Pappa, Sahika Inal, Kirsty Roy, Yi Zhang, Charalampos Pitsalidis, Adel Hama, Jolien Pas, George G Malliaras, Roisin M Owens
Oppositely charged polyelectrolyte multilayers (PEMs) were built-up in a layer-by-layer (LbL) assembly on top of the conducting polymer channel of an organic electrochemical transistor (OECT), aiming to combine the advantages of well-established PEMs with a high performance electronic transducer. The multilayered film is a model system to investigate the impact of biofunctionalization on the operation of OECTs comprising a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) film as the active layer...
March 6, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28259560/4-chlorophenylguanidine-is-an-asic3-agonist-and-positive-allosteric-modulator
#8
Amruta S Agharkar, Eric B Gonzales
Acid-sensing ion channels (ASICs) are proton-sensitive sodium channels that open in response to lowered extracellular pH and are expressed in the central and peripheral nervous systems. The ASIC3 subtype is found primarily in the periphery where the channel mediates pain signals caused by ischemia and inflammation. Here, we provide identify 4-chlorophenylguanidine (4-CPG) as an ASIC3 positive allosteric modulator and newest member of the growing group of guanidine modulators of ASICs. Furthermore, the 4-CPG reversed the effects of ASIC3 desensitization...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28254778/regulation-of-stomatal-immunity-by-interdependent-functions-of-a-pathogen-responsive-mpk3-mpk6-cascade-and-abscisic-acid
#9
Jianbin Su, Mengmeng Zhang, Lawrence Zhang, Tiefeng Sun, Yidong Liu, Wolfgang Lukowitz, Juan Xu, Shuqun Zhang
Activation of mitogen-activated protein kinases (MAPKs) is one of the earliest responses after plants sense an invading pathogen. Here we show that MPK3 and MPK6, two Arabidopsis thaliana pathogen-responsive MAPKs, and their upstream MAPK Kinases, MKK4 and MKK5, are essential to both stomatal and apoplastic immunity. Loss of function of MPK3 and MPK6, or their upstream MKK4 and MKK5, abolishes pathogen/microbe-associated molecular pattern- and pathogen-induced stomatal closure. Gain-of-function activation of MPK3/MPK6 induces stomatal closure independently of abscisic acid (ABA) biosynthesis and signaling...
March 2, 2017: Plant Cell
https://www.readbyqxmd.com/read/28237818/quercetin-inhibits-acid-sensing-ion-channels-through-a-putative-binding-site-in-the-central-vestibular-region
#10
Mohona Mukhopadhyay, Anurag Singh, S Sachchidanand, Amal Kanti Bera
Acid-sensing ion channels (ASICs) are associated with many pathophysiological processes, such as neuronal death during ischemic stroke, epileptic seizure and nociception. However, there is a dearth of ASIC-specific therapeutic blockers. Here we report that quercetin, a plant flavonoid, which is known for its neuroprotective effect, reversibly inhibits homomeric rat ASIC1a, ASIC2a and ASIC3 with an IC50 of about 2µM. Also, quercetin prevents low pH-induced intracellular calcium rise and cell death in HEK-293 cells, which have endogenous expression of ASIC1a and 2a...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28212011/a-fluorescent-anionic-mof-with-zn4-trz-2-chain-for-highly-selective-visual-sensing-of-contaminants-cr-iii-ion-and-tnp
#11
Xiao-Xia Jia, Ru-Xin Yao, Fu-Qiang Zhang, Xian-Ming Zhang
Heavy-metal ions and nitroaromatic substances are highly toxic and harmful to human health and the ecological environment. It is an urgent issue to selectively detect and capture these toxic substances. By introducing the triazole ligand to the π-conjugated aromatic carboxylate system and borrowing the organic template open framework idea, a stable fluorescent framework [Me2NH2]4[Zn6(qptc)3(trz)4]·6H2O (1) (H4qptc = terphenyl-2,5,2'5'-tetracarboxylic acid, trz = 1,2,4-triazole) has been successfully synthesized, which features Zn4(trz)2 chain-based 3D anionic structure with channels filled by [Me2NH2](+) cations...
February 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28211811/acidity-and-acid-sensing-ion-channels-in-the-normal-and-alzheimer-s-disease-brain
#12
Eric B Gonzales, Nathalie Sumien
Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28193786/bile-acids-potentiate-proton-activated-currents-in-xenopus-laevis-oocytes-expressing-human-acid-sensing-ion-channel-asic1a
#13
Alexandr V Ilyaskin, Alexei Diakov, Christoph Korbmacher, Silke Haerteis
Acid-sensing ion channels (ASICs) are nonvoltage-gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin (DEG) family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid-sensitive ion channel (BASIC) and ENaC. To investigate whether bile acids also modulate ASIC function, human ASIC1a was heterologously expressed in Xenopus laevis oocytes. Exposing oocytes to tauro-conjugated cholic (t-CA), deoxycholic (t-DCA), and chenodeoxycholic (t-CDCA) acid at pH 7...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28187208/respiratory-virus-infection-up-regulates-trpv1-trpa1-and-asics3-receptors-on-airway-cells
#14
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/28181561/peripheral-sensory-neuron-injury-contributes-to-neuropathic-pain-in-experimental-autoimmune-encephalomyelitis
#15
I-Ching Wang, Chen-Yen Chung, Fang Liao, Chih-Cheng Chen, Cheng-Han Lee
Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159907/acid-sensing-ion-channels-activated-by-evoked-released-protons-modulate-synaptic-transmission-at-the-mouse-calyx-of-held-synapse
#16
Carlota González-Inchauspe, Francisco J Urbano, Mariano N Di Guilmi, Osvaldo D Uchitel
Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward currents (IASIC) in postsynaptic MNTB neurons from wild type (WT) mice. The inhibition of IASIC by psalmotoxin-1 (PcTx1) and the absence of these currents in knock out mice for ASIC-1a subunit (ASIC1a(-/-)) suggest that homomeric ASIC-1a channels are mediating these currents in MNTB neurons...
February 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28137639/acid-sensing-ion-channel-1a-is-required-for-mglu-receptor-dependent-long-term-depression-in-the-hippocampus
#17
D Mango, E Braksator, G Battaglia, S Marcelli, N B Mercuri, M Feligioni, F Nicoletti, Z I Bashir, R Nisticò
Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na(+) channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca(2+) and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS)...
January 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28121219/amiloride-sensitive-cation-channel-2-genotype-affects-the-response-to-a-carbon-dioxide-panic-challenge
#18
Nicole K Leibold, Daniel LA van den Hove, Wolfgang Viechtbauer, Gunter Kenis, Liesbet Goossens, Iris Lange, Inge Knuts, Hubert J Smeets, Inez Myin-Germeys, Harry Wm Steinbusch, Koen Rj Schruers
Until recently, genetic research into panic disorder (PD) has had only limited success. Inspired by rodent research, demonstrating that the acid-sensing ion channel 1a (ASIC1a) is critically involved in the behavioral fear response to carbon dioxide (CO2) exposure, variants in the human homologue gene amiloride-sensitive cation channel 2 (ACCN2) were shown to be associated with PD. However, the relationship between changes in brain pH and ACCN2, as done in rodents by CO2 exposure, has not been investigated yet in humans...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28117962/acidotoxicity-via-asic1a-mediates-cell-death-during-oxygen-glucose-deprivation-and-abolishes-excitotoxicity
#19
Saurav Bhowmick, Jeanette T Moore, Daniel L Kirschner, Mary C Curry, Emily G Westbrook, Brian T Rasley, Kelly L Drew
Ischemia-reperfusion (I/R) injury is associated with a complex and multifactorial cascade of events involving excitotoxicity, acidotoxicity, and ionic imbalance. While it is known that acidosis occurs concomitantly with glutamate-mediated excitotoxicity during brain ischemia, it remains elusive, how acidosis-mediated acidotoxicity interacts with glutamate-mediated excitotoxicity. Here, we investigated the effect of acidosis on glutamate-mediated excitotoxicity in acute hippocampal slices. We tested the hypothesis that mild acidosis protects against I/R injury via modulation of NMDAR, but produces injury via activation of acid sensing ion channels (ASIC1a)...
January 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28111260/down-regulation-of-asic1-suppressed-gastric-cancer-via-inhibiting-autophagy
#20
Qiong Zhang, Shiwu Wu, Jinhai Zhu, Damin Chai, Huaiyong Gan
As autophagy has anti-apoptosis effect and accelerates cell survival, many studies start to target autophagy as a therapeutic strategy for cancer. Acid-sensing ion channels (ASICs) was reported to activate autophagy. However, whether ASICs can regulate gastric cancer through autophagy is unknown. The differentially expressed genes in normal gastric tissue and gastric cancer tissue in patients were investigated by RNA-seq. Expression of ASIC1 and autophagy related 5 (ATG5) was further confirmed by real-time PCR...
April 15, 2017: Gene
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