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https://www.readbyqxmd.com/read/28797116/calcium-imaging-with-genetically-encoded-sensor-case12-facile-analysis-of-%C3%AE-7-%C3%AE-9-nachr-mutants
#1
Irina Shelukhina, Ekaterina Spirova, Denis Kudryavtsev, Lucy Ojomoko, Markus Werner, Christoph Methfessel, Michael Hollmann, Victor Tsetlin
Elucidation of the structural basis of pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs) may shed light on their involvement in different physiological functions and diseases. Combination of site-directed mutagenesis and electrophysiology is a powerful tool to pinpoint the key amino-acid residues in the receptor ligand-binding site, but for α7 and α9 nAChRs it is complicated by their poor expression and fast desensitization. Here, we probed the ligand-binding properties of α7/α9 nAChR mutants by a proposed simple and fast calcium imaging method...
2017: PloS One
https://www.readbyqxmd.com/read/28796387/ulinastatin-inhibited-sepsis-induced-spinal-inflammation-to-alleviate-peripheral-neuromuscular-dysfunction-in-an-experimental-rat-model-of-neuromyopathy
#2
Fei Xie, Su Min, Jingyuan Chen, Jun Yang, Xin Wang
Sepsis initiates a neuroinflammatory cascade that contributes to spinal cord inflammation and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In this study, we tested the hypothesis that ulinastatin (ULI) inhibits sepsis-induced spinal inflammation to alleviate peripheral neuromuscular dysfunction through the TLR4/MyD88/NF-κB signaling pathway. Muscular function, spinal cord water content, and cytokine levels of spinal cord were tested in TLR4-inhibited rats subjected to cecal ligation and puncture (CLP)...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28791704/granulocytes-as-models-for-human-protein-marker-identification-following-nicotine-exposure
#3
REVIEW
Matthew J Mulcahy, Henry A Lester
Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian CNS, in the peripheral nervous system, and in skeletal muscle. Neuronal-type nAChRs are also found in several non-neuronal cell types, including leukocytes. Granulocytes are a subtype of leukocytes that include basophils, eosinophils, and neutrophils. Granulocytes, also known as polymorphonuclear leukocytes, are characterized by their ability to produce, store, and release compounds from intracellular granules...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28791474/acetylcholine-nicotinic-receptor-subtypes-in-chromaffin-cells
#4
REVIEW
Manuel Criado
In the adrenal gland, acetylcholine released on stimulation of the sympathetic splanchnic nerve activates neuronal-type nicotinic receptors (nAChRs) in chromaffin cells and triggers catecholamine secretion. At least two subtypes of nAChRs have been described in bovine chromaffin cells. The main subtype, a heteromeric assembly of α3, β4 and perhaps α5 subunits, is involved in the activation step of the catecholamine secretion process and is not blocked by the snake toxin α-bungarotoxin. The other is α-bungarotoxin-sensitive, and its functional role has not yet been well defined...
August 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28781257/-possible-involvement-of-neuronal-nicotinic-acetylcholine-receptors-in-compensatory-brain-mechanisms-at-early-stages-of-parkinson-s-disease
#5
E V Kryukova, I V Shelukhina, A A Kolacheva, A Kh Alieva, M I Shadrina, P A Slominsky, I E Kasheverov, Y N Utkin, M V Ugrumov, V I Tsetlin
A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson's disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative determination of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, -conotoxin MII, and -bungarotoxin as ligands. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28780166/5-desmethylnobiletin-augments-synaptic-ach-levels-and-nicotinic-ach-receptor-activity-a-potential-candidate-for-alleviation-of-cholinergic-dysfunction
#6
Shalini Trivedi, Priyanka Maurya, Shreesh Raj Sammi, Madan Mohan Gupta, Rakesh Pandey
Cholinergic function is compromised in plethora of neurodegenerative disorders especially Alzheimer's disease. Increasing acetylcholine (ACh) levels has been the mainstay in majority of the therapeutic regimens, accepted for management of disease. The present study investigates the efficacy of 5-Desmethylnobiletin (DN), a polymethoxyflavone in augmenting cholinergic function using Caenorhabditis elegans as a model organism. The studies revealed significant elevation in cholinergic transmission mediated through increased levels of ACh and activity of nicotinic acetylcholine receptors (nAChR)...
August 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28770361/exploring-the-binding-energy-profiles-of-full-agonists-partial-agonists-and-antagonists-of-the-%C3%AE-7-nicotinic-acetylcholine-receptor
#7
Nargis Tabassum, Qianyun Ma, Guanzhao Wu, Tao Jiang, Rilei Yu
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure...
September 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28766701/rationale-for-an-adjunctive-therapy-with-fenofibrate-in-pharmacoresistant-nocturnal-frontal-lobe-epilepsy
#8
Monica Puligheddu, Miriam Melis, Giuliano Pillolla, Giulia Milioli, Liborio Parrino, Giovanni Mario Terzano, Sonia Aroni, Claudia Sagheddu, Francesco Marrosu, Marco Pistis, Anna Lisa Muntoni
OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR...
August 2, 2017: Epilepsia
https://www.readbyqxmd.com/read/28763248/evaluating-commercially-available-antibodies-for-rat-%C3%AE-7-nicotinic-acetylcholine-receptors
#9
Brijesh K Garg, Ralph H Loring
Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) are important drug targets in neurological disorders and inflammation, making their detection and localization by validated antibodies highly desirable. However, tests in knockout animals raised questions about specificity of antibodies to mouse α7 nAChRs. To date, methods for validating antibodies for rat or human α7 nAChR have not been reported. We developed a gel-shift assay for western blots using GH4C1 cells expressing either native rat receptors or α7 nAChR-green fluorescent protein (GFP) chimeras to evaluate seven commercially available α7 nAChR antibodies...
August 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#10
Wuyi Liu, Ming D Li
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system...
August 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28759616/altered-nicotine-reward-associated-behavior-following-%C3%AE-4-nachr-subunit-deletion-in-ventral-midbrain
#11
Can Peng, Staci E Engle, Yijin Yan, Marcus M Weera, Jennifer N Berry, Matthew C Arvin, Guiqing Zhao, J Michael McIntosh, Julia A Chester, Ryan M Drenan
Nicotinic acetylcholine receptors containing α4 subunits (α4β2* nAChRs) are critical for nicotinic cholinergic transmission and the addictive action of nicotine. To identify specific activities of these receptors in the adult mouse brain, we coupled targeted deletion of α4 nAChR subunits with behavioral and and electrophysiological measures of nicotine sensitivity. A viral-mediated Cre/lox approach allowed us to delete α4 from ventral midbrain (vMB) neurons. We used two behavioral assays commonly used to assess the motivational effects of drugs of abuse: home-cage oral self-administration, and place conditioning...
2017: PloS One
https://www.readbyqxmd.com/read/28755692/two-distinctive-%C3%AE-subunits-are-separately-involved-in-two-binding-sites-of-imidacloprid-with-different-affinities-in-locusta-migratoria-manilensis
#12
Haibo Bao, Yang Liu, Yixi Zhang, Zewen Liu
Due to great diversity of nicotinic acetylcholine receptor (nAChR) subtypes in insects, one β subunit may be contained in numerous nAChR subtypes. In the locust Locusta migratoria, a model insect species with agricultural importance, the third β subunits (Locβ3) was identified in this study, which reveals at least three β subunits in this insect species. Imidacloprid was found to bind nAChRs in L. migratoria central nervous system at two sites with different affinities, with Kd values of 0.16 and 10.31nM...
August 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28754351/the-alpha-7-nicotinic-acetylcholine-receptor-is-involved-in-a-direct-inhibitory-effect-of-nicotine-on-gnrh-release-in-vitro-studies
#13
Elio Messi, Federica Pimpinelli, Valentina Andrè, Chiara Rigobello, Cecilia Gotti, Roberto Maggi
The activation of nicotinic cholinergic receptors (nAChR) inhibits the reproductive axis; however, it is not clear whether nicotine may directly modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH). Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of a single class of high affinity α4β2 and α7 nAchR subtypes. The exposure of GT1-1 cells to nicotine does not modify the basal accumulation of GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion experiments and inhibits, the release of GnRH induced by prostaglandin E1 or by K(+)-induced cell depolarization; these effects were reversed by D-tubocurarine and α-bungarotoxin...
July 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28750889/reciprocal-activation-of-%C3%AE-5-nachr-and-stat3-in-nicotine-induced-human-lung-cancer-cell-proliferation
#14
Yao Zhang, Yanfei Jia, Ping Li, Huanjie Li, Dongjie Xiao, Yunshan Wang, Xiaoli Ma
Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors (nAChRs). Genome-wide association studies (GWAS) show that CHRNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 (pSTAT3) expression, smoking history and lower survival of non-small cell lung cancer (NSCLC) samples...
July 20, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28735558/nicotinic-receptor-abnormalities-in-the-cerebellar-cortex-of-sudden-unexplained-fetal-and-infant-death-victims-possible-correlation-with-maternal-smoking
#15
Anna M Lavezzi, Stefano Ferrero, Luca Roncati, Francesco Piscioli, Luigi Matturri, Teresa Pusiol
Nicotinic acetylcholine receptors (nAChRs) are cationic channels of the neuronal cell membrane, differentially expressed in the central nervous system which, when activated by endogenous acetylcholine or exogenous nicotine, are able to enhance cholinergic transmission. The aim of this study was to investigate in human perinatal age the immunohistochemical expression of the α7-nAChR subtype, given its involvement in neuronal differentiation and its significant vulnerability to the toxic effects of nicotine...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28731133/irrelevance-of-anti%C3%A2-nachr-cytoplasmic-loop-antibody-in-the-degree-of-myasthenia-gravis
#16
Ye Lin, Chen Song, Jiang Xu, Yongxiang Yang, Hang Qin, Cong Zhao, Jiaji Lin, Rui Liu, Zhuyi Li
Anti‑nicotinic acetylcholine receptor (nAChR) antibody in myasthenia gravis (MG) usually refers to that against the extracellular domain (ECD) of nAChR. However, growing evidence has indicated that there also exists the nAChR antibody against the nAChR cytoplasmic loop (CL) in patients with MG. Some studies have demonstrated that the anti‑CL antibody may play a protective role in animal models of experimental autoimmune MG. However, to date, limited or no information is available as to whether anti‑CL antibody plays a beneficial role in patients with MG...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28726253/%C3%AE-9-and-%C3%AE-7-containing-receptors-mediate-the-pro-proliferative-effects-of-nicotine-in-the-a549-adenocarcinoma-cell-line
#17
Vanessa Mucchietto, Francesca Fasoli, Susanna Pucci, Milena Moretti, Roberta Benfante, Annalisa Maroli, Simona Di Lascio, Cristiano Bolchi, Marco Pallavicini, Cheryl Dowell, Michael McIntosh, Francesco Clementi, Cecilia Gotti
BACKGROUND AND PURPOSE: Tobacco smoke contains many classes of carcinogens and although nicotine is unable to initiate tumorigenesis in humans and rodents, it promotes tumour growth and metastasis in lung tumours by acting on neuronal nicotinic acetylcholine receptors (nAChRs). The aim of this study was to identify molecularly, biochemically and pharmacologically which nAChR subtypes are expressed and functionally activated by nicotine in lung cancer cell lines. EXPERIMENTAL APPROACH: We used A549 and H1975 adenocarcinoma cell lines derived from lung tumour to test the in vitro effects of nicotine, and nAChR subtype-specific peptides and compounds...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28725182/canonical-and-novel-non-canonical-cholinergic-agonists-inhibit-atp-induced-release-of-monocytic-interleukin-1%C3%AE-via-different-combinations-of-nicotinic-acetylcholine-receptor-subunits-%C3%AE-7-%C3%AE-9-and-%C3%AE-10
#18
Anna Zakrzewicz, Katrin Richter, Alisa Agné, Sigrid Wilker, Kathrin Siebers, Bijan Fink, Gabriela Krasteva-Christ, Mike Althaus, Winfried Padberg, Arik J Hone, J Michael McIntosh, Veronika Grau
Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1β (IL-1β) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of α7, α9 and/or α10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits α9 and α10...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28718820/a-transcriptomic-survey-of-ion-channel-based-conotoxins-in-the-chinese-tubular-cone-snail-conus-betulinus
#19
Yu Huang, Chao Peng, Yunhai Yi, Bingmiao Gao, Qiong Shi
Conotoxins in the venom of cone snails (Conus spp.) are a mixture of active peptides that work as blockers, agonists, antagonists, or inactivators of various ion channels. Recently we reported a high-throughput method to identify 215 conotoxin transcripts from the Chinese tubular cone snail, C. betulinus. Here, based on the previous datasets of four transcriptomes from three venom ducts and one venom bulb, we explored ion channel-based conotoxins and predicted their related ion channel receptors. Homologous analysis was also performed for the most abundant ion channel protein, voltage-gated potassium (Kv; with Kv1...
July 18, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28718646/exploring-the-relationship-between-nicotinic-acetylcholine-receptor-ligand-size-efficiency-efficacy-and-c-loop-opening
#20
Qianyun Ma, Han-Shen Tae, Guanzhao Wu, Tao Jiang, Rilei Yu
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels mediating fundamental physiological activities in the nervous system and have become important targets for drug design. For a long time, the acetylcholine binding protein (AChBP) has been used as a surrogate to study the nAChR structure-function. Taking advantage of more than 100 AChBP crystal structures in the Protein DataBank (PDB), we explored the relationship between the size, efficiency, and efficacy of nAChR ligands and the C-loop movement...
August 2, 2017: Journal of Chemical Information and Modeling
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