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https://www.readbyqxmd.com/read/28532679/the-functional-interaction-between-nicotinic-acetylcholine-receptors-and-ly-6-neurotoxin-proteins-in-locusta-migratoria
#1
Haibo Bao, Yixi Zhang, Yang Liu, Na Yu, Zewen Liu
Failures in expressing insect nAChRs (nicotinic acetylcholine receptors) limit the understanding of their functional properties, although insect nAChRs have been developed as insecticide targets for decades. Some accessory proteins can modulate nAChRs, but only a few have been identified in insects, including lynx from Ly-6/neurotoxin superfamily. Until now, only one to three lynx were identified in one insect species. Here, 11 lynx were identified in Locusta migratoria with common features of Ly-6/neurotoxin members...
May 19, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28529765/signals-of-vagal-circuits-engaging-with-akt1-in-%C3%AE-7-nachr-cd11b-cells-lessen-e-coli-and-lps-induced-acute-inflammatory-injury
#2
Caiqi Zhao, Xi Yang, Emily M Su, Yuanyuan Huang, Ling Li, Michael A Matthay, Xiao Su
Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by Chrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate E. coli and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR(+)CD11b(+) cells (CD11b is coded by Itgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28527955/neuroprotective-effect-of-the-alpha-7-nicotinic-receptor-agonist-pha-543613-in-an-in-vivo-excitotoxic-adult-rat-model
#3
Laura Foucault-Fruchard, Aurélie Doméné, Guylène Page, Marguerite Windsor, Patrick Emond, Nuno Rodrigues, Frédéric Dollé, Annelaure Damont, Frédéric Buron, Sylvain Routier, Sylvie Chalon, Daniel Antier
Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. A preliminary study was performed in vitro to confirm PHA 543613 agonist properties on α7nAChRs...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28521453/nicotine-may-promote-tongue-squamous-cell-carcinoma-progression-by-activating-the-wnt-%C3%AE-catenin-and-wnt-pcp-signaling-pathways
#4
Chengze Wang, Xin Xu, Hairu Jin, Gangli Liu
To investigate the effects and the possible underlying mechanisms of nicotine stimulation on tongue squamous cell carcinoma (TSCC) progression, a TSCC cell line Cal27 and 34 samples of paraffin-embedded TSCC were examined. Immunofluorescence, western blot analysis, and TOP/FOP flash, CCK-8, wound healing and Transwell invasion assays were used to evaluate Cal27 in response to nicotine stimulation. We also investigated expression levels of related proteins of Wnt/β-catenin and Wnt/PCP pathways in paraffin-embedded TSCC samples with or without a history of smoking by immunohistochemistry...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28507032/%C3%AE-2-nicotinic-acetylcholine-receptors-influence-hippocampus-dependent-learning-and-memory-in-adolescent-mice
#5
Shahrdad Lotfipour, Celina Mojica, Sakura Nakauchi, Marcela Lipovsek, Sarah Silverstein, Jesse Cushman, James Tirtorahardjo, Andrew Poulos, Ana Belén Elgoyhen, Katumi Sumikawa, Michael S Fanselow, Jim Boulter
The absence of α2* nicotinic acetylcholine receptors (nAChRs) in oriens lacunosum moleculare (OLM) GABAergic interneurons ablate the facilitation of nicotine-induced hippocampal CA1 long-term potentiation and impair memory. The current study delineated whether genetic mutations of α2* nAChRs (Chrna2(L9'S/L9'S) and Chrna2(KO)) influence hippocampus-dependent learning and memory and CA1 synaptic plasticity. We substituted a serine for a leucine (L9'S) in the α2 subunit (encoded by the Chrna2 gene) to make a hypersensitive nAChR...
June 2017: Learning & Memory
https://www.readbyqxmd.com/read/28499726/inhibitory-effect-of-donepezil-on-bradykinin-induced-increase-in-the-intracellular-calcium-concentration-in-cultured-cortical-astrocytes
#6
Kouki Makitani, Shota Nakagawa, Yasuhiko Izumi, Akinori Akaike, Toshiaki Kume
Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca(2+)]i) in cultured astrocytes. Bradykinin-induced [Ca(2+)]i increase was inhibited by the exposure to thapsigargin, which depletes Ca(2+) stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca(2+)...
April 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28498560/deletion-of-%C3%AE-5-nicotine-receptor-subunits-abolishes-nicotinic-aversive-motivational-effects-in-a-manner-that-phenocopies-dopamine-receptor-antagonism
#7
Taryn E Grieder, Olivier George, Mandy Yee, Michael A Bergamini, Michal Chwalek, Geith Maal-Bared, Hector Vargas-Perez, Derek van der Kooy
Nicotine addiction is a worldwide epidemic that claims millions of lives each year. Genetic deletion of α5 nicotinic acetylcholine receptor (nAChR) subunits has been associated with increased nicotine intake, however, it remains unclear whether acute nicotine is less aversive or more rewarding, and whether mice lacking the α5 nAChR subunit can experience withdrawal from chronic nicotine. We used place conditioning and conditioned taste avoidance paradigms to examine the effect of α5 subunit-containing nAChR deletion (α5 -/-) on conditioned approach and avoidance behaviour in nondependent and nicotine-dependent and -withdrawn mice, and compared these motivational effects with those elicited after dopamine receptor antagonism...
May 12, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28496137/tumor-suppressor-menin-is-required-for-subunit-specific-nachr-%C3%AE-5-transcription-and-nachr-dependent-presynaptic-facilitation-in-cultured-mouse-hippocampal-neurons
#8
Angela M Getz, Fenglian Xu, Frank Visser, Roger Persson, Naweed I Syed
In the central nervous system (CNS), cholinergic transmission induces synaptic plasticity that is required for learning and memory. However, our understanding of the development and maintenance of cholinergic circuits is limited, as the factors regulating the expression and clustering of neuronal nicotinic acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our group have implicated calpain-dependent proteolytic fragments of menin, the product of the MEN1 tumor suppressor gene, in coordinating the transcription and synaptic clustering of nAChRs in invertebrate central neurons...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28496108/alpha7-nicotinic-acetylcholine-receptor-agonist-promotes-retinal-ganglion-cell-function-via-modulating-gabaergic-presynaptic-activity-in-a-chronic-glaucomatous-model
#9
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494644/the-alpha-7-nicotinic-acetylcholine-receptor-of-deciduous-dental-pulp-stem-cells-regulates-osteoclastogenesis-during-physiological-root-resorption
#10
Lulu Wang, Zhifei Zhou, Yujiang Chen, Shuai Yuan, Yang Du, Xinke Ju, Lizheng Wu, Xiaojing Wang
The physiological root resorption of deciduous teeth is a normal phenomenon, but the mechanisms underlying this process are still unclear. In this study, deciduous dental pulp stem cells (DDPSCs) and permanent dental pulp stem cells (DPSCs) were derived from deciduous teeth and normal permanent teeth at different stages of resorption. In the middle stage of root resorption, DDPSCs exhibited an increase in the ability to induce osteoclast differentiation. Activation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) by secretory mammalian Ly-6 urokinase-type plasminogen activator receptor-associated protein 1 (SLURP-1) caused a significant increase in the expression levels of NF-κB, RANKL and the ratio of RANKL/OPG...
May 11, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28494312/anagyrine-desensitization-of-peripheral-nicotinic-acetylcholine-receptors-a-potential-biomarker-of-quinolizidine-alkaloid-teratogenesis-in-cattle
#11
Benedict T Green, Stephen T Lee, Kevin D Welch, Daniel Cook
Anagyrine, a teratogenic quinolizidine alkaloid found in Lupinus spp., is proposed to undergo metabolism by pregnant cattle to a piperidine alkaloid which inhibits fetal movement, the putative mechanism behind crooked calf syndrome. The objective of this study was to test the hypothesis that anagyrine but not lupanine or sparteine can directly, without metabolism, desensitize nicotinic acetylcholine receptors (nAChR) in a cell culture model. SH-SY5Y cells expressing autonomic nAChR, and TE-671 cells expressing fetal muscle-type nAChR were exposed to lupine alkaloids or Dimethylphenylpiperazinium (DMPP) in log10 molar increments from 10nM to 100μM and then to a fixed concentration of acetylcholine (ACh) (10μM for SH-SY5Y cells and 1μM for TE-671 cells) and the responses measured with a membrane potential sensing dye to assess nAChR activation and desensitization...
May 2, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28494140/identification-of-%C3%AE-7-nicotinic-acetylcholine-receptor-silent-agonists-based-on-the-spirocyclic-quinuclidine-%C3%AE-2-isoxazoline-scaffold-synthesis-and-electrophysiological-evaluation
#12
Clelia Mariangiola Luisa Dallanoce, Marta Quadri, Carlo Matera, Almin Silnović, Maria Chiara Pismataro, Nicole Alana Horenstein, Clare Stokes, Roger Lee Papke
Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model ligand for the design of new silent agonists of α7 nAChRs. Silent agonists evoke little or no channel activation but can induce the α7 desensitized Ds state, sensitive to a type II positive allosteric modulator (PAM) such as PNU-120596. Introduction of meta-substituents into the benzyloxy moiety of 11 led to the two sets of tertiary amines and quaternary ammonium salts based on the spirocyclic quinuclidinyl-Δ2-isoxazoline scaffold...
May 11, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28487481/functional-genomics-in-brugia-malayi-reveal-diverse-muscle-nachrs-and-differences-between-cholinergic-anthelmintics
#13
Saurabh Verma, Sudhanva Srinivas Kashyap, Alan Patrick Robertson, Richard John Martin
Many techniques for studying functional genomics of important target sites of anthelmintics have been restricted to Caenorhabditis elegans because they have failed when applied to animal parasites. To overcome these limitations, we have focused our research on the human nematode parasite Brugia malayi, which causes elephantiasis. Here, we combine single-cell PCR, whole muscle cell patch clamp, motility phenotyping (Worminator), and dsRNA for RNAi for functional genomic studies that have revealed, in vivo, four different muscle nAChRs (M-, L-, P-, and N-)...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28479061/crystal-structures-of-human-glyr%C3%AE-3-bound-to-ivermectin
#14
Xin Huang, Hao Chen, Paul L Shaffer
Ivermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), γ-aminobutyric acid receptors (GABAARs), glycine receptors (GlyRs), and neuronal α7-nicotinic receptors (α7 nAChRs). The crystal structure of Caenorhabditis elegans GluCl complexed with ivermectin revealed the details of its ivermectin binding site. Although the electron microscopy structure of zebrafish GlyRα1 complexed with ivermectin demonstrated a similar binding orientation, detailed structural information on the ivermectin binding and pore opening for Cys-loop receptors in vertebrates has been elusive...
May 4, 2017: Structure
https://www.readbyqxmd.com/read/28477386/persistent-activation-of-%C3%AE-7-nachrs-associated-with-stable-induction-of-different-desensitized-states
#15
Roger L Papke, Clare Stokes, M Imad Damaj, Ganesh A Thakur, Khan Manther, Millet Treinin, Deniz Bagdas, Abhijit R Kulkarni, Nicole A Horenstein
BACKGROUND AND PURPOSE: GAT107 is a positive allosteric modulator and agonist (ago-PAM) of α7 nicotinic acetylcholine receptors that can cause a prolonged period of primed potentiation of acetylcholine responses after drug washout. NS6740 is a silent agonist of α7 that has little or no efficacy for activating the ion channel but induces stable desensitization states, some of which can be converted into channel-active states by PAMs. Although GAT107 and NS6740 appear to stably induce different non-conducting states, interestingly, both agents have been shown to be effective treatment for inflammation and inflammatory pain models...
May 6, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28477355/%C3%AE-conotoxins-active-at-%C3%AE-3-containing-nicotinic-acetylcholine-receptors-and-their-molecular-determinants-for-selective-inhibition
#16
REVIEW
Hartmut Cuny, Rilei Yu, Han-Shen Tae, Shiva N Kompella, David J Adams
Neuronal α3-containing nicotinic acetylcholine receptors (nAChRs) in the peripheral nervous system (PNS) and non-neuronal tissues are implicated in a number of severe disease conditions ranging from cancer to cardiovascular diseases, and chronic pain. However, despite the physiological characterization of mouse models and cell lines, the precise pathophysiology of nAChRs outside the central nervous system (CNS) remains not well understood, in part because there is a lack of subtype-selective antagonists. α-Conotoxins isolated from cone snail venom exhibit characteristic individual selectivity profiles for nAChRs and, therefore, are excellent tools to study the determinants for nAChR-antagonist interactions...
May 6, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28472227/cortical-nnos-nk1-receptor-neurons-are-regulated-by-cholinergic-projections-from-the-basal-forebrain
#17
Rhîannan H Williams, Jacqueline Vazquez-DeRose, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
Cholinergic (ACh) basal forebrain (BF) neurons are active during wakefulness and rapid eye movement (REM) sleep and are involved in sleep homeostasis. We have previously shown in adult animals that cortical neurons that express neuronal nitric oxide synthase (nNOS) and the receptor for Substance P (NK1R) are activated during non-REM (NREM) sleep in proportion to homeostatic sleep drive. Here, we show that BF neurons modulate cortical nNOS/NK1R cells. In vitro optogenetic stimulation of BF terminals both activated and inhibited nNOS/NK1R neurons...
May 2, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28460123/use-of-electronic-cigarettes-leads-to-significant-beta2-nicotinic-acetylcholine-receptor-occupancy-evidence-from-a-pet-imaging-study
#18
Stephen R Baldassarri, Ansel T Hillmer, Jon Mikael Anderson, Peter Jatlow, Nabeel Nabulsi, David Labaree, Kelly P Cosgrove, Stephanie S O'Malley, Thomas Eissenberg, Suchitra Krishnan-Sarin, Irina Esterlis
Background: Electronic cigarettes (ECs) can influence nicotine addiction by delivering aerosolized nicotine. We investigated if nicotine from ECs is delivered to the brain β2*-nicotinic-acetylcholine receptors (β2*-nAChR) and how this relates to the behavioral effects and nicotine delivery from cigarettes. Methods: Seven nicotine users participated in positron emission tomography (PET) studies with (-)-[18F]Flubatine before and after nicotine challenge with 0, 8 mg/ml, and 36 mg/ml nicotine in a 3...
April 29, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28457878/the-t-type-calcium-channel-enhancer-sak3-inhibits-neuronal-death-following-transient-brain-ischemia-via-nicotinic-acetylcholine-receptor-stimulation
#19
Yasushi Yabuki, Xu Jing, Kohji Fukunaga
The T-type calcium channel enhancer SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo[1,2-a]pyridin]-2-ene-3-carboxylate) promotes acetylcholine (ACh) release in mouse hippocampus, enhancing cognitive function. Here, we tested SAK3 neuroprotective activity in the context of transient brain ischemia using a 20-min bilateral common carotid arteries occlusion (BCCAO) mouse model. Mice were administered with SAK3 (0.1, 0.5 or 1.0 mg/kg, p.o.) 24 h after BCCAO ischemia. Oral SAK3 (0...
April 27, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28457669/%C3%AE-6%C3%AE-2-nicotinic-acetylcholine-receptors-influence-locomotor-activity-and-ethanol-consumption
#20
Helen M Kamens, Colette Peck, Caitlin Garrity, Alex Gechlik, Brenita C Jenkins, Akshat Rajan
Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have been implicated in ethanol behaviors. In particular, work in genetically engineered mice has demonstrated that α6-containing nAChRs are involved in ethanol consumption and sedation. A limitation of these studies is that the alteration in the receptor was present throughout development. The recently described α6β2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), now makes it possible to test for the involvement of these receptors using a pharmacological approach...
April 27, 2017: Alcohol
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