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The important role of Acetylcholine

Luiz Renato Olchanheski, Regina Sordi, Junior Garcia Oliveira, Gustavo Ferreira Alves, Reila Taina Mendes, Fábio André Santos, Daniel Fernandes
OBJECTIVE: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. MATERIAL AND METHODS: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34)...
October 4, 2018: Journal of Applied Oral Science: Revista FOB
Serge Sicouri, Luiz Belardinelli, Charles Antzelevitch
INTRODUCTION: Extrasystoles arising from the muscular sleeves associated with pulmonary veins (PV), superior vena cava (SVC) and coronary sinus (CS) are known to precipitate atrial fibrillation (AF). The late sodium channel current (INa ) inhibitor ranolazine has been reported to exert antiarrhythmic effects in canine PV and SVC sleeves by suppressing late phase 3 early and delayed afterdepolarization (EAD and DAD)-induced triggered activity induced by parasympathetic and/or sympathetic stimulation...
October 9, 2018: Journal of Cardiovascular Electrophysiology
Artur Jan Kiepura, Andrzej Kochański
Charcot‑Marie‑Tooth type 1A (CMT1A) is a dysmyelinating disease of the peripheral nervous system that results in a slow progressive weakening and wasting of the distal muscles of the upper and lower limbs. Despite extensive research and clinical trials there is still no treatment for CMT1A that results in complete neurological improvement. Recent studies investigating various pharmacological modulators of adenylyl cyclase activity, including ascorbic acid and ligands of G protein‑coupled receptors (GPCRs), provide hope for future treatments of this type of hereditary motor and sensory neuropathy...
2018: Acta Neurobiologiae Experimentalis
Benoit Forget, Petra Scholze, Francina Langa, Carole Morel, Stephanie Pons, Sarah Mondoloni, Morgane Besson, Romain Durand-de Cuttoli, Audrey Hay, Ludovic Tricoire, Bertrand Lambolez, Alexandre Mourot, Philippe Faure, Uwe Maskos
Tobacco addiction is a chronic and relapsing disorder with an important genetic component that represents a major public health issue. Meta-analysis of large-scale human genome-wide association studies (GWASs) identified a frequent non-synonymous SNP in the gene coding for the α5 subunit of nicotinic acetylcholine receptors (α5SNP), which significantly increases the risk for tobacco dependence and delays smoking cessation. To dissect the neuronal mechanisms underlying the vulnerability to nicotine addiction in carriers of the α5SNP, we created rats expressing this polymorphism using zinc finger nuclease technology and evaluated their behavior under the intravenous nicotine-self-administration paradigm...
September 26, 2018: Current Biology: CB
Dong-Jie Li, Jie Tong, Fei-Yan Zeng, Mengqi Guo, Yong-Hua Li, Hongbo Wang, Pei Wang
BACKGROUND AND PURPOSE: Platelet-derived growth factor-BB (PDGF-BB) is an angiogenic factor involved in cardiovascular diseases. Here, we investigated the possible effects of activation of nicotinic acetylcholine receptor α7 subtype (α7nAChR) on PDGF-BB-induced proliferation and migration in vascular smooth muscle cells (VSMCs). EXPERIMENTAL APPROACH: PNU-282987, a selective α7nAChR pharmacological agonist, was used to activate α7nAChR. The influences of α7nAChR activation on PDGF-BB-induced proliferation and migration, as well as the phosphorylation of focal adhesion kinase/Src, a pro-migration signaling pathway, were determined in VSMCs...
September 30, 2018: British Journal of Pharmacology
Yuka Saito, Masato Mashimo, Akari Nobeyama, Kana Murakami, Takeshi Fujii
Lymphocytic cholinergic system has important roles in T cell functions, including immune responses and proliferation and differentiation of immune cells. T lymphocytes exclusively produces acetylcholine (ACh) via choline acetyltransferase (ChAT), activating their muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively) in an autocrine and paracrine manners. Hippocampal cholinergic neurostimulating peptide (HCNP) is an undecapeptide cleaved from N-terminal of phosphatidylethanolamine-binding protein 1 (PEBP1)...
2018: Biological & Pharmaceutical Bulletin
Arnav Kumar, Olivia Y Hung, Marina Piccinelli, Parham Eshtehardi, Michel T Corban, David Sternheim, Boyi Yang, Adrien Lefieux, David S Molony, Elizabeth W Thompson, Wenjie Zeng, Yasir Bouchi, Sonu Gupta, Hossein Hosseini, Mohamad Raad, Yi-An Ko, Chang Liu, Michael C McDaniel, Bill D Gogas, John S Douglas, Arshed A Quyyumi, Don P Giddens, Alessandro Veneziani, Habib Samady
OBJECTIVES: The study investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx). BACKGROUND: Local hemodynamic forces such as WSS play an important role in atherogenesis through their effect on endothelial cells. The study hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD). METHODS: Forty-four patients with CAD underwent coronary angiography, fractional flow reserve, and endothelial function testing...
September 19, 2018: JACC. Cardiovascular Interventions
Abdul-Fattah Salah Fararjeh, Shih-Hsin Tu, Li-Ching Chen, Tzu-Chun Cheng, Yun-Ru Liu, Hang-Lung Chang, Hui-Wen Chang, Chi-Cheng Huang, Hwa-Chain Robert Wang, Wendy W Hwang-Verslues, Chih-Hsiung Wu, Yuan-Soon Ho
Breast cancer (BC) is the most common cancer affecting women worldwide and has been associated with active tobacco smoking. Low levels of nicotine (Nic) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have been detected in cases of second-hand smoke (SHS). However, the correlation between SHS and BC risk remains controversial. In this study, we investigated whether the physiological SHS achievable dose of Nic and tobacco specific nitrosamine, NNK act together to induce breast carcinogenesis using an in vitro breast cell carcinogenesis model...
September 26, 2018: Environmental Toxicology
Jinpeng Yu, Xiaopeng Zhu, Peta J Harvey, Quentin Kaas, Dongting Zhangsun, David J Craik, Sulan Luo
The α3β4 nicotinic acetylcholine receptor (nAChR) is an important target implicated in various disease states. α-Conotoxin TxID (1) is the most potent antagonist of α3β4 nAChR, but it also exhibits inhibition of α6/α3β4 nAChR. The results of alanine scanning of 1 suggested a vital role for Ser9 in the selectivity of the peptide. In this study, Ser9 was substituted with a series of 14 amino acids, including some non-natural amino acids, displaying different physicochemical characteristics to further improve the selectivity of 1 toward α3β4 nAChR...
October 9, 2018: Journal of Medicinal Chemistry
Márcia Vagos, Ilsbeth G M van Herck, Joakim Sundnes, Hermenegild J Arevalo, Andrew G Edwards, Jussi T Koivumäki
The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications...
2018: Frontiers in Physiology
Youssouf Cissé, Hanieh Toossi, Masaru Ishibashi, Lynda Mainville, Christopher S Leonard, Antoine Adamantidis, Barbara E Jones
Acetylcholine (ACh) neurons in the pontomesencephalic tegmentum (PMT) are thought to play an important role in promoting cortical activation with waking (W) and paradoxical sleep [PS; or rapid eye movement (REM)], but have yet to be proven to do so by selective stimulation and simultaneous recording of identified ACh neurons. Here, we employed optogenetics combined with juxtacellular recording and labeling of neurons in transgenic (TG) mice expressing ChR2 in choline acetyltransferase (ChAT)-synthesizing neurons...
July 2018: ENeuro
Ee Von Moo, Patrick M Sexton, Arthur Christopoulos, Celine Valant
Muscarinic acetylcholine receptors (mAChRs) are exemplar models for understanding G protein-coupled receptor (GPCR) allostery, possessing a "common" allosteric site in an extracellular vestibule (ECV) for synthetic modulators including gallamine, strychnine, and brucine. In addition, there is intriguing evidence of endogenous peptides/proteins that may target this region at the M2 mAChR. A common feature of synthetic and endogenous M2 mAChR negative allosteric modulators (NAMs) is their cationic nature...
November 2018: Molecular Pharmacology
Shu Wang, Yanan Jiang, Jingling Chen, Changliang Dai, Dandan Liu, Wei Pan, Lijuan Wang, Moyondafoluwa Blessing Fasae, Lihua Sun, Lanfeng Wang, Yan Liu
BACKGROUND/AIMS: Because the prevalence of age-related cardiac impairment increases as the human lifespan increases, it is important to combat the effects of aging. Recently, the cardiac M3 muscarinic acetylcholine receptor (M3-mAChR) has been demonstrated to play important roles in cardiac development and in the pathogenesis of cardiac diseases. However, the role of M3-mAChR in aging remains largely unknown. Therefore, the aim of this study was to investigate the involvement of M3-mAChR in the progression of cardiac aging...
2018: Cellular Physiology and Biochemistry
Shunichi Gamo, Tsutomu Tamada, Koji Murakami, Soshi Muramatsu, Hidemi Aritake, Masayuki Nara, Itsuro Kazama, Tatsuma Okazaki, Hisatoshi Sugiura, Masakazu Ichinose
NEW FINDINGS: What is the central question of this study? Does Toll-like receptor 7 (TLR7) have any direct effects on Ca2+ -dependent physiological function of tracheal submucosal gland cells? What is the main finding and its importance? TLR7 is co-localized with SERCA2 in tracheal submucosal gland cells and causes a rapid attenuation of acetylcholine (ACh)-induced, Ca2+ -dependent ionic currents through the activation of SERCA2-dependent Ca2+ clearance. TLR7 is abundantly expressed in the airways of both swine and healthy human subjects, but is significantly downregulated in chronic obstructive pulmonary disease (COPD) airways...
September 8, 2018: Experimental Physiology
Matthew A Tucker, Kathryn Taylor, Rozina Merchant, Sharon George, Caroline Stoddard, Kevin Kopera
It has been proposed that normal waking levels of acetylcholine (ACH) are important for initial memory acquisition, and that decreased ACH is critical for memory consolidation. Sleep is thought to benefit memory consolidation in part due to the predominance of low ACH levels observed during non-rapid eye movement sleep. Here we examined whether sleep and ACH suppression with the cholinergic antagonist scopolamine impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness...
August 30, 2018: Neurobiology of Learning and Memory
Yu-Juan Zhou, Hao Zhao, Ying Wang, Jing Yu, Liang Tian, Jing Wang
The vestibular center of the brainstem contains afferent and efferent vestibular neurons, which play an important role in information perception, processing, and sensory integration. Vestibular efferent neurons (VENs) can receive changes in vestibular afferent information and regulate peripheral vestibular function; however, it remains unclear how VENs change after vestibular afferent information increases or weakens. In this study, we used animal models with altered vestibular afferent information by electrically stimulating or destroying the vestibular medial nucleus (MVe)...
October 17, 2018: Neuroreport
Jie Su, Xing-Rong An, Qing Li, Xiao-Xue Li, Xiao-Dong Cong, Ming Xu
Endothelial cell apoptosis plays an important role in the pathophysiological mechanism of vascular complications in type 2 diabetes mellitus (T2DM). Argirein, a new synthetic compound was demonstrated to inactivate NADPH oxidase to alleviate cardiac dysfunction in T2DM. Here, we investigated whether argirein medication attenuated the vascular dysfunction in T2DM by inhibiting endothelial cell apoptosis which was associated with NADPH oxidase. The rat aortic endothelial cells (RAECs) were incubated with glucose (30 mM) for 48 hour in vitro...
August 22, 2018: Scientific Reports
Stephanie C Dulawa, David S Janowsky
Mood disorders are highly prevalent and are the leading cause of disability worldwide. The neurobiological mechanisms underlying depression remain poorly understood, although theories regarding dysfunction within various neurotransmitter systems have been postulated. Over 50 years ago, clinical studies suggested that increases in central acetylcholine could lead to depressed mood. Evidence has continued to accumulate suggesting that the cholinergic system has a important role in mood regulation. In particular, the finding that the antimuscarinic agent, scopolamine, exerts fast-onset and sustained antidepressant effects in depressed humans has led to a renewal of interest in the cholinergic system as an important player in the neurochemistry of major depression and bipolar disorder...
August 17, 2018: Molecular Psychiatry
Katrin Richter, Sabrina Sagawe, Andreas Hecker, Mira Küllmar, Ingolf Askevold, Jelena Damm, Sarah Heldmann, Michael Pöhlmann, Sophie Ruhrmann, Michael Sander, Klaus-Dieter Schlüter, Sigrid Wilker, Inke R König, Wolfgang Kummer, Winfried Padberg, Arik J Hone, J Michael McIntosh, Anna Teresa Zakrzewicz, Christian Koch, Veronika Grau
Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently measured as a clinical marker for inflammation, but the biological functions of CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin, mainly produced in the liver in response to elevated levels of interleukin-1β (IL-1β) and of the IL-1β-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1β levels can cause life-threatening diseases such as trauma-associated systemic inflammation...
2018: Frontiers in Immunology
Carla Roberta Nunes Polachini, Roselia Maria Spanevello, Maria Rosa Chitolina Schetinger, Vera Maria Morsch
Multiple sclerosis (MS) commonly affects young adults and leads to a decreased quality of life due to different signs and symptoms that induce physical, cognitive, social, and psychological challenges. This disease, an autoimmune neurological disorder, is characterized by chronic inflammatory demyelination and axonal degeneration of the central nervous system (CNS). To date, its etiology is unknown. A large number of physiological functions are regulated by the cholinergic system because the acetylcholine (ACh) is released from cholinergic neurons and acts on other neurons, most of them not cholinergic in the brain, as well as in various nonneuronal cells, such as those of the immune system and blood; thus, it is considered an important modulatory pathway of both the central and peripheral nervous systems...
September 15, 2018: Journal of the Neurological Sciences
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