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nicotine neuromuscular

Franziska Wild, Muzamil Majid Khan, Tatjana Straka, Rüdiger Rudolf
Endocytosed nicotinic acetylcholine receptors (CHRN) are degraded via macroautophagy/autophagy during atrophic conditions and are accompanied by the autophagic regulator protein SH3GLB1. The present study addressed the functional role of SH3GLB1 on CHRN trafficking and its implementation. We found an augmented ratio of total SH3GLB1 to threonine-145 phosphorylated SH3GLB1 (SH3GLB1:p-SH3GLB1) under conditions of increased CHRN vesicle numbers. Overexpression of T145 phosphomimetic (T145E) and phosphodeficient (T145A) mutants of SH3GLB1, were found to either slow down or augment the processing of endocytic CHRN vesicles, respectively...
October 7, 2016: Autophagy
Mohamed B Abou-Donia, Briana Siracuse, Natasha Gupta, Ashly Sobel Sokol
Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i...
October 5, 2016: Critical Reviews in Toxicology
Rui Fan, Ruirui Ji, Wenxin Zou, Guoliang Wang, Hu Wang, Daniel James Penney, Jin Jun Luo, Yuxin Fan
Andersen-Tawil syndrome (ATS) is an autosomal dominant, multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias and distinctive dysmorphic facial or skeletal features. The disorder displays marked intrafamilial variability and incomplete penetrance. Myasthenia gravis (MG) is an autoimmune disorder that demonstrates progressive fatigability, in which the nicotinic acetylcholine receptor (AChR) at neuromuscular junctions is the primary autoantigen. The present study reports a rare case of a 31-year-old woman with a history of morbid obesity and periodic weakness, who presented with hemodynamic instability, cardiogenic shock and facial anomalies...
October 2016: Experimental and Therapeutic Medicine
Claudio L Morales-Perez, Colleen M Noviello, Ryan E Hibbs
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century. In addition to the receptors' prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery...
October 3, 2016: Nature
Masayuki Homma, Akiyuki Uzawa, Hitoshi Tanaka, Naoki Kawaguchi, Tetsuya Kanai, Kenji Nakajima, Masakuni Narita, Yukio Hara, Hideya Maruyama, Yasumasa Ogawa, Keiichi Himuro, Satoshi Kuwabara
Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG...
September 27, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Hayato Terayama, Hitoshi Endo, Hideo Tsukamoto, Koichi Matsumoto, Mai Umezu, Teruhisa Kanazawa, Masatoshi Ito, Tadayuki Sato, Munekazu Naito, Satoshi Kawakami, Yasuhiro Fujino, Masayuki Tatemichi, Kou Sakabe
Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported...
2016: International Journal of Environmental Research and Public Health
William Dalkin, Thomas Taetzsch, Gregorio Valdez
The neuromuscular junction (NMJ) undergoes deleterious structural and functional changes as a result of aging, injury and disease. Thus, it is imperative to understand the cellular and molecular changes involved in maintaining and repairing NMJs. For this purpose, we have developed a method to reliably and consistently examine regenerating NMJs in mice. This nerve injury method involves crushing the common fibular nerve as it passes over the lateral head of the gastrocnemius muscle tendon near the knee. Using 70 day old female mice, we demonstrate that motor axons begin to reinnervate previous postsynaptic targets within 7 days post-crush...
2016: Journal of Visualized Experiments: JoVE
Aurélie Couesnon, Rómulo Aráoz, Bogdan I Iorga, Evelyne Benoit, Morgane Reynaud, Denis Servent, Jordi Molgó
The cyclic imine toxin 20-methyl spirolide G (20-meSPX-G), produced by the toxigenic dinoflagellate Alexandrium ostenfeldii/Alexandrium peruvianum, has been previously reported to contaminate shellfish in various European coastal locations, as revealed by mouse toxicity bioassay. The aim of the present study was to determine its toxicological profile and its molecular target selectivity. 20-meSPX-G blocked nerve-evoked isometric contractions in isolated mouse neuromuscular preparations, while it had no action on contractions elicited by direct electrical stimulation, and reduced reversibly nerve-evoked compound muscle action potential amplitudes in anesthetized mice...
2016: Toxins
Christiane G Stäuble, Marc Helming, J A Jeevendra Martyn, Manfred Blobner, Heidrun Fink
OBJECTIVES: Recovery from ICU-acquired muscle weakness extends beyond hospital stay. We hypothesized that immobilization, more than inflammation, plays a prominent role in the delayed recovery from critical illness. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal laboratory, university hospital. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Animals were divided to have one hind limb immobilized (n = 129) or sham-immobilized (n = 129) on day -12...
November 2016: Critical Care Medicine
Hai-Feng Li, Yu Hong, Xu Zhang, Yanchen Xie, Geir Olve Skeie, Hong-Jun Hao, Nils Erik Gilhus, Bing Liang, Yao-Xian Yue, Xian-Jun Zhang, Xiang Gao, Qi Wang, Zhe Gao, Xiao-Jun Ding, Min Song
Myasthenia gravis (MG) is an antibody-mediated autoimmune disease against antigens at the neuromuscular junction. Both genetic and environmental factors contribute to the susceptibility of MG. We undertook a case-control study to explore the contribution of genes of the auto-antigen and immune-modulating proteins in the pathogenesis of MG. We enrolled 389 adult MG patients and 487 healthy controls. Eighteen SNPs were selected from genes of cholinergic receptor nicotinic alpha 1 (CHRNA1), autoimmune regulator (AIRE), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), protein tyrosine phosphatase nonreceptor type 22 (PTPN22), and interleukin-10 (IL-10)...
August 8, 2016: Molecular Neurobiology
Noemí Mañé, Verónica Jiménez-Sábado, Marcel Jiménez
P2Y1 receptors mediate nerve mediated purinergic inhibitory junction potentials (IJP) and relaxations in the gastrointestinal (GI) tract in a wide range of species including rodents and humans. A new P2Y1 antagonist, with a non-nucleotide structure, BPTU, has recently been described using X-ray crystallography as the first allosteric G-protein-coupled receptor antagonist located entirely outside of the helical bundle. In this study, we tested its effect on purinergic responses in the gastrointestinal tract of rodents using electrophysiological and myographic techniques...
November 2016: Neuropharmacology
D Gunasekaran, J Sridhar, V Suryanarayanan, N C Manimaran, Sanjeev Kumar Singh
Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS)...
July 15, 2016: Journal of Biomolecular Structure & Dynamics
I V Kovyazina, A N Tsentsevitsky, E E Nikolsky
Experiments on frog neuromuscular junctions have demonstrated that asynchrony of the acetylcholine quantal release forming the multi-quantal evoked response at high-frequency synaptic activity is caused, in particular, by a decrease in velocity of the action potential propagation along the non-myelinated nerve endings, which is mediated by activation of the α7 and α4β4 nicotinic cholinoreceptors.
May 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
Benedict T Green, Stephen T Lee, Kevin D Welch, Daniel Cook, William R Kem
Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate...
2016: Toxins
Jørgen S Agerholm, Fintan J McEvoy, Fiona Menzi, Vidhya Jagannathan, Cord Drögemüller
BACKGROUND: Bovine arthrogryposis multiplex congenita (AMC) is a syndromic term for a congenital condition characterized by multiple joint contractures. Rare inherited forms of bovine AMC have been reported in different breeds. For AMC in Angus cattle a causative genomic deletion encompassing the agrin (AGRN) gene, encoding an essential neural regulator that induces the aggregation of acetylcholine receptors (AChRs), is known. In 2015, three genetically related cases of generalized AMC affecting Red dairy calves were diagnosed in Denmark...
2016: BMC Genomics
Bojana Kravic, Danyil Huraskin, Alexander D Frick, Jasmin Jung, Veronika Redai, Ralf Palmisano, Sylvie Marchetto, Jean-Paul Borg, Lin Mei, Said Hashemolhosseini
Erbin, Lano, Scribble, and Densin-180 belong to LAP [leucine-rich repeats (LRRs) and PDZ domain] adaptor proteins involved in cell signaling pathways. Previously, we identified Erbin, Lano and Scribble, but not Densin-180, in muscle cells, where they are involved in regulating the aggregation of nicotinic acetylcholine receptors (AChR) in vitro. Here, we analysed their cellular localization at the neuromuscular junction (NMJ) in skeletal muscles of mice. Erbin, Lano and Scribble were significantly accumulated at NMJs and localized in different synaptic cells...
June 20, 2016: Journal of Neurochemistry
D Zhang, D Wang, I I Pipinos, R L Muelleman, Y-L Li
AIM: Tourniquet-induced ischaemia and subsequent reperfusion cause serious ischaemia-reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long-term functional recovery of the NMJ and skeletal muscle in tourniquet-induced hindlimb IR. METHODS: Unilateral hindlimb of C57/BL6 mice was subjected to 3 h of ischaemia following 6 weeks of reperfusion (6-wk IR). Dex treatment began on the day of IR induction and lasted for different periods...
June 16, 2016: Acta Physiologica
Steven B Bird, Predrag Krajacic, Keigo Sawamoto, Naofumi Bunya, Emanuele Loro, Tejvir S Khurana
Organophosphorus (OP) pesticide poisoning is a leading cause of morbidity and mortality in the developing world, affecting an estimated three million people annually. Much of the morbidity is directly related to muscle weakness, which develops 1-4 days after poisoning. This muscle weakness, termed the intermediate syndrome (IMS), leads to respiratory, bulbar, and proximal limb weakness and frequently necessitates the use of mechanical ventilation. While not entirely understood, the IMS is most likely due to persistently elevated acetylcholine (ACh), which activates nicotinic ACh receptors at the neuromuscular junction (NMJ)...
June 2016: Annals of the New York Academy of Sciences
Yusuke Miyazaki, Hiroshi Sunaga, Shotaro Hobo, Kazuko Miyano, Shoichi Uezono
PURPOSE: This study was conducted to elucidate the mechanism of enhancement of volatile anesthetics by neuromuscular blocking agents in rats and to consider the relevance of this enhancement to clinical anesthesia. METHODS: Male Sprague-Dawley rats were used. After confirming a movement in response to tail clamping under 1.1 % isoflurane anesthesia, response was determined when the tail clamp was applied at several points after microinjection of pancuronium into the lateral ventricle...
August 2016: Journal of Anesthesia
Hai-Peng Huang, Hong Pan, Hong-Feng Wang
Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction...
March 2016: Neural Regeneration Research
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