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acetylcholine

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https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#1
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905548/neurexin-regulates-nighttime-sleep-by-modulating-synaptic-transmission
#2
Huawei Tong, Qian Li, Zi Chao Zhang, Yi Li, Junhai Han
Neurexins are cell adhesion molecules involved in synaptic formation and synaptic transmission. Mutations in neurexin genes are linked to autism spectrum disorders (ASDs), which are frequently associated with sleep problems. However, the role of neurexin-mediated synaptic transmission in sleep regulation is unclear. Here, we show that lack of the Drosophila α-neurexin homolog significantly reduces the quantity and quality of nighttime sleep and impairs sleep homeostasis. We report that neurexin expression in Drosophila mushroom body (MB) αβ neurons is essential for nighttime sleep...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905515/neonicotinoid-induced-impairment-of-odour-coding-in-the-honeybee
#3
Mara Andrione, Giorgio Vallortigara, Renzo Antolini, Albrecht Haase
Exposure to neonicotinoid pesticides is considered one of the possible causes of honeybee (Apis mellifera) population decline. At sublethal doses, these chemicals have been shown to negatively affect a number of behaviours, including performance of olfactory learning and memory, due to their interference with acetylcholine signalling in the mushroom bodies. Here we provide evidence that neonicotinoids can affect odour coding upstream of the mushroom bodies, in the first odour processing centres of the honeybee brain, i...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904031/variant-aldehyde-dehydrogenase-2-aldh2-2-in-east-asians-interactively-exacerbates-tobacco-smoking-risk-for-coronary-spasm%C3%A3-possible-role-of-reactive-aldehydes
#4
Yuji Mizuno, Seiji Hokimoto, Eisaku Harada, Kenji Kinoshita, Michihiro Yoshimura, Hirofumi Yasue
BACKGROUND: Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS andALDH2*2as a risk factor for CSA to better understand the disease pathogenesis.Methods and Results:The study subjects comprised 410 patients (258 men, 152 women; mean age, 66...
November 29, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27901080/block-of-nicotinic-acetylcholine-receptors-by-philanthotoxins-is-strongly-dependent-on-their-subunit-composition
#5
Hamid S Kachel, Rohit N Patel, Henrik Franzyk, Ian R Mellor
Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899792/nature-nurtures-the-design-of-new-semi-synthetic-macrolide-antibiotics
#6
REVIEW
Prabhavathi Fernandes, Evan Martens, David Pereira
Erythromycin and its analogs are used to treat respiratory tract and other infections. The broad use of these antibiotics during the last 5 decades has led to resistance that can range from 20% to over 70% in certain parts of the world. Efforts to find macrolides that were active against macrolide-resistant strains led to the development of erythromycin analogs with alkyl-aryl side chains that mimicked the sugar side chain of 16-membered macrolides, such as tylosin. Further modifications were made to improve the potency of these molecules by removal of the cladinose sugar to obtain a smaller molecule, a modification that was learned from an older macrolide, pikromycin...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27899739/impact-of-immune-deficiency-on-remodeling-of-maternal-resistance-vasculature-4-weeks-postpartum-in-mice
#7
Elizabeth A Bonney, Ann Howard, Kendall Krebs, Kelly Begin, Kelsey Veilleux, Natalia I Gokina
Pregnancy manifests changes in the vascular and immune systems that persist postpartum (PP), have important implications for future pregnancies, and may modify responses to cardiovascular stress in late life. The association between immune and vascular function and the generation or progression of cardiovascular disease beg the question of whether altered immunity modifies pregnancy-induced changes in the vasculature. Our objective was to compare changes in the function and remodeling of systemic resistance vessels 4 weeks PP in normal C57BL/6 (B6), and immunodeficient mice recombinase 1-deficient/B6 (Rag1(-/-))...
November 28, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27899232/expression-of-muscarinic-acetylcholine-receptors-in-hepatocytes-from-rat-fibrotic-liver
#8
Lin Luo, Tingting Xu, Pengbo Wang, Liuliu Mao, Chenghao Xi, Jinhua Huang, Wei Zhang
The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated...
November 26, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27897258/lack-of-fibronectin-extra-domain-a-alternative-splicing-exacerbates-endothelial-dysfunction-in-diabetes
#9
Gianluca Gortan Cappellari, Rocco Barazzoni, Luigi Cattin, Andrés F Muro, Michela Zanetti
Glucose-induced changes of artery anatomy and function account for diabetic vascular complications, which heavily impact disease morbidity and mortality. Since fibronectin containing extra domain A (EDA + FN) is increased in diabetic vessels and participates to vascular remodeling, we wanted to elucidate whether and how EDA + FN is implicated in diabetes-induced endothelial dysfunction using isometric-tension recording in a murine model of diabetes. In thoracic aortas of EDA(-/-), EDA(+/+) (constitutively lacking and expressing EDA + FN respectively), and of wild-type mice (EDA(wt/wt)), streptozotocin (STZ)-induced diabetes impaired endothelial vasodilation to acetylcholine, irrespective of genotype...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896932/mesoionic-insecticides-a-novel-class-of-insecticides-that-modulate-nicotinic-acetylcholine-receptors
#10
Caleb W Holyoke, Daniel Cordova, Wenming Zhang, James D Barry, Robert M Leighty, Robert F Dietrich, James J Rauh, Thomas F Pahutski, George P Lahm, My-Hanh Thi Tong, Eric A Benner, John L Andreassi, Rejane M Smith, Daniel R Vincent, Laurie A Christianson, Luis A Teixeira, Vineet Singh, Kenneth A Hughes
BACKGROUND: As the world population grows toward 9 billion by 2050 it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields due to pests. Development of new insecticides will help sustain this protection and overcome insecticide resistance. RESULTS: A novel class of mesoionic compounds has been discovered with exceptional insecticidal activity on a range of Hemiptera and Lepidoptera...
November 29, 2016: Pest Management Science
https://www.readbyqxmd.com/read/27895434/bay-41-2272-treatment-improves-acetylcholine-induced-aortic-relaxation-in-l-name-hypertensive-rats
#11
Shahid Prawez, Azad Ahmad Ahanger, Thakur Uttam Singh, Santosh Kumar Mishra, Souvendra Nath Sarkar, Dinesh Kumar
Hypertension, an emerging problem of recent era, and many pathophysiological factors are participating to produce the disease. Nitric oxide (NO) is an important constituent to ameliorate hypertensive condition. Inhibition of endogenous NO synthase by L-N(G)-Nitroarginine methyl ester (L-NAME) was responsible for generating hypertension in rats. BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine), a soluble guanylyl cyclase activator, restricts rise of blood pressure and shows cardioprotective activity...
December 2016: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/27895421/carbon-monoxide-contributes-to-the-constipating-effects-of-granisetron-in-rat-colon
#12
Carmela Nacci, Margherita Fanelli, Maria Assunta Potenza, Valentina Leo, Monica Montagnani, Maria Antonietta De Salvia
AIM: To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of granisetron. METHODS: For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50 μg/kg/intraperitoneal (ip)] and hemin (50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27895161/the-e-loop-of-the-transmitter-binding-site-is-a-key-determinant-of-the-modulatory-effects-of-physostigmine-on-neuronal-nicotinic-%C3%AE-4%C3%AE-2-receptors
#13
Xiaochun Jin, Megan M McCollum, Allison L Germann, Gustav Akk, Joseph H Steinbach
Physostigmine is a well-known inhibitor of acetylcholinesterase, which can also activate, potentiate and inhibit acetylcholine receptors, including neuronal nicotinic receptors comprising α4 and β2 subunits. We have found that the two stoichiometric forms of this receptor differ in the effects of physostigmine. The form containing 3 copies of α4 and 2 of β2 was potentiated at low concentrations of ACh and physostigmine, while the form containing 2 copies of α4 and 3 of β2 was inhibited. Chimeric constructs of subunits indicated that the presence of inhibition or potentiation depended on the source of the extracellular ligand-binding domain of the subunit...
November 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27894093/new-use-of-an-old-drug-inhibition-of-breast-cancer-stem-cells-by-benztropine-mesylate
#14
Jihong Cui, Maija Hollmén, Lina Li, Yong Chen, Steven T Proulx, Daniel Reker, Gisbert Schneider, Michael Detmar
Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells)...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893014/durability-of-the-rituximab-response-in-acetylcholine-receptor-autoantibody-positive-myasthenia-gravis
#15
Kimberly R Robeson, Aditya Kumar, Benison Keung, Daniel B DiCapua, Emily Grodinsky, Huned S Patwa, Panos A Stathopoulos, Jonathan M Goldstein, Kevin C O'Connor, Richard J Nowak
Importance: Myasthenia gravis (MG), an autoimmune disorder of neuromuscular transmission, is treated by an array of immunotherapeutics, many of which are nonspecific. Even with current therapies, a subset of patients has medically refractory MG. The benefits of B-cell-targeted therapy with rituximab have been observed in MG; however, the duration of these benefits after treatment is unclear. Objective: To evaluate the durability of response to rituximab in the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG...
November 21, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27891689/deficit-in-acoustic-signal-in-noise-detection-in-glycine-receptor-%C3%AE-3-subunit-knockout-mice
#16
Konstantin Tziridis, Stefanie Buerbank, Volker Eulenburg, Julia Dlugaiczyk, Holger Schulze
Hearing is an essential sense for communication in animals and humans. Normal function of the cochlea of higher vertebrates relies on a fine-tuned interplay of afferent and efferent innervation of both inner and outer hair cells. Efferent inhibition is controlled via olivocochlear feedback loops, mediated mainly by acetylcholine, γ-aminobutyric acid (GABA) and glycine, and is one of the first sites affected by synapto- and neuropathy in the development of hearing loss. While the functions of acetylcholine, GABA, and other inhibitory transmitters within these feedback loops are at least partially understood, especially the function of glycine still remains elusive...
November 27, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27891095/differential-rna-expression-profile-of-skeletal-muscle-induced-by-experimental-autoimmune-myasthenia-gravis-in-rats
#17
Henry J Kaminski, Keiichi Himuro, Jumana Alshaikh, Bendi Gong, Georgiana Cheng, Linda L Kusner
The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27890007/a-current-perspective-on-the-inhibition-of-cholinesterase-by-natural-and-synthetic-inhibitors
#18
Anzer A Shah, Showkat A Ganie, Mohammad A Kamal, Tanveer Ali Dar
Majority of the observed cognitive and behavioral changes in Alzheimer's diseaseare postulated to be due to the deficiencies in cholinergic pathways of the brain. Enhancement of cholinergic transmission may thus stimulate the cholinergic receptors or prolong the availability of acetylcholine in synaptic cleft and hence improve the Alzheimer's disease associated symptoms. Of these two, the inhibition of cholinesterases (Acetylcholinesterase and Butyrylcholinesterase) by cholinesterase inhibitors is suggested to be a promising strategy...
November 23, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27889925/deletion-of-the-vesicular-acetylcholine-transporter-from-pedunculopontine-laterodorsal-tegmental-neurons-modifies-gait
#19
Helena Janickova, Kaie Rosborough, Mohammed Al-Onaizi, Ornela Kljakic, Monica S Guzman, Robert Gros, Marco A M Prado, Vania F Prado
Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signalling in the brainstem. We investigated how long-term loss of cholinergic signalling from mesopontine nuclei influence motor behaviours. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChT(E)(n1-Cre-flox/flox) )...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27886889/update-on-ocular-myasthenia-gravis
#20
REVIEW
Stacy V Smith, Andrew G Lee
Ocular myasthenia gravis (OMG) is a localized form of myasthenia gravis in which autoantibodies directed against acetylcholine receptors block or destroy these receptors at the postsynaptic neuromuscular junction. The hallmark of OMG is a history of painless weakness or fatigability of the extraocular muscles and ptosis with normal pupillary function and visual acuity. Clinical, laboratory, electrophysiologic, and pharmacologic tests are available for diagnosis. Treatment can begin with symptom management; there is no cure...
February 2017: Neurologic Clinics
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