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The important role of Acetylcholine

Qingsong Lin, Lingyun Zhao, Ran Jing, Christa Trexler, Hong Wang, Yali Li, Huayuan Tang, Fang Huang, Fei Zhang, Xi Fang, Jie Liu, Nan Jia, Ju Chen, Kunfu Ouyang
Background Endothelial NO synthase plays a central role in regulating vasodilation and blood pressure. Intracellular Ca2+ mobilization is a critical modulator of endothelial NO synthase function, and increased cytosolic Ca2+ concentration in endothelial cells is able to induce endothelial NO synthase phosphorylation. Ca2+ release mediated by 3 subtypes of inositol 1,4,5-trisphosphate receptors ( IP 3 Rs) from the endoplasmic reticulum and subsequent Ca2+ entry after endoplasmic reticulum Ca2+ store depletion has been proposed to be the major pathway to mobilize Ca2+ in endothelial cells...
February 19, 2019: Journal of the American Heart Association
Leniz F Nurullin, Venera F Khuzakhmetova, Eduard F Khaziev, Dmitry V Samigullin, Andrei N Tsentsevitsky, Andrei I Skorinkin, Ellya A Bukharaeva, Olga Vagin
Septins are highly conserved GTP-binding cytoskeletal proteins involved in neuronal signaling in central nervous system but their involvement in signal transmission in peripheral synapses remains unclear. Sept5 and Sept9 proteins were detected in mouse peripheral neuromuscular junctions by immunofluorescence with a greater degree of colocalization with presynaptic than postsynaptic membranes. Preincubation of neuromuscular junction preparations with the inhibitor of septin dynamics, forchlorfenuron (FCF), decreased co-localization of septins with presynaptic membranes...
February 7, 2019: Neuroscience
Maureen A Cox, Gordon S Duncan, Gloria H Y Lin, Benjamin E Steinberg, Lisa X Yu, Dirk Brenner, Luke N Buckler, Andrew J Elia, Andrew C Wakeham, Brian Nieman, Carmen Dominguez-Brauer, Alisha R Elford, Kyle T Gill, Shawn P Kubli, Jillian Haight, Thorsten Berger, Pamela S Ohashi, Kevin J Tracey, Peder S Olofsson, Tak W Mak
Although widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection...
February 8, 2019: Science
Nabeel B Nabulsi, Daniel Holden, Ming-Qianq Zheng, Frederic Bois, Shu-Fei Lin, Soheila Najafzadeh, Hong Gao, Jim Ropchan, Teresa Lara-Jaime, David Labaree, Anupama Shirali, Lawrence J Slieker, Cynthia D Jesudason, Vanessa N Barth, Antonio Navarro, Nancy Kant, Richard E Carson, Henry Huang
The M1 muscarinic acetylcholine receptor (mAChR) plays an important role in learning and memory, and therefore is a target for development of drugs for treatment of cognitive impairments in Alzheimer's disease and schizophrenia. The availability of M1-selective radiotracers for positron emission tomography (PET) will help in developing therapeutic agents by providing an imaging tool for assessment of drug dose-receptor occupancy relationship. Here we report the synthesis and evaluation of 11 C-LSN3172176 (ethyl 4-(6-(methyl-11 C)-2-oxoindolin-1-yl)-[1,4'-bipiperidine]-1'-carboxylate) in non-human primates...
February 7, 2019: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Jin Shuai Liu, Zong Jie Cui
Although methionine sulfoxide reductase (Msr) is known to modulate the activity of multiple functional proteins, the roles of Msr in pancreatic stellate cell physiology have not been reported. In the present work we investigated expression and function of Msr in freshly isolated and cultured rat pancreatic stellate cells. Msr expression was determined by RT-PCR, Western blot and immunocytochemistry. Msr over-expression was achieved by transfection with adenovirus vectors. Pancreatic stellate cells were co-cultured with pancreatic acinar cells AR4-2J in monolayer culture...
February 1, 2019: Cells
Akiyo Ito, Takashi Shiroto, Shigeo Godo, Hiroki Saito, Shuhei Tanaka, Yosuke Ikumi, Shoko Kajitani, Kimio Satoh, Hiroaki Shimokawa
Although increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of cardiovascular diseases, the importance of physiological ROS has also been emerging. We have previously demonstrated that endothelium-derived hydrogen peroxide (H2 O2 ) is one of endothelium-dependent hyperpolarization (EDH) factors and that loss of endothelial caveolin-1 reduces EDH/H2 O2 in microcirculation. Caveolin-1 (Cav-1) is a scaffolding/ regulatory protein that interacts with diverse signaling pathways including angiogenesis...
February 1, 2019: American Journal of Physiology. Heart and Circulatory Physiology
Sebastian Meller, Claudia Brandt, Wiebke Theilmann, Jochen Klein, Wolfgang Löscher
Chemically or electrically induced status epilepticus (SE) in rodents is a commonly used method for induction of epilepsy. Structural and functional changes in the hippocampus play a pivotal role in epileptogenesis induced by SE. Although cholinergic mechanisms have long been thought to play an important role in the onset and propagation of epileptic seizures, not much is known about the potential role of acetylcholine (ACh) in ictogenesis and epileptogenesis in SE models of temporal lobe epilepsy. Here we used in vivo microdialysis to determine extracellular levels of ACh and, for comparison, several amino acid transmitters in the ventral hippocampus during SE, epileptogenesis, and the chronic epileptic state in two rat models of SE-induced epilepsy...
January 28, 2019: Brain Research
Yuichi Saito, Hideki Kitahara, Takeshi Nishi, Yoshihide Fujimoto, Yoshio Kobayashi
OBJECTIVES: Coronary endothelial and circulatory dysfunction plays important roles in the pathogenesis of vasospastic angina (VSA). However, a complete understanding of the entire coronary circulation including microvasculature in patients with VSA is lacking. PATIENTS AND METHODS: A total of 32 patients without obstructive coronary artery disease in the left descending coronary artery, who underwent an intracoronary acetylcholine (ACh) provocation test for diagnosis of VSA, were enrolled prospectively...
January 29, 2019: Coronary Artery Disease
Khalil Hajiasgharzadeh, Saeed Sadigh-Eteghad, Behzad Mansoori, Ahad Mokhtarzadeh, Dariush Shanehbandi, Mohammad Amin Doustvandi, Zahra Asadzadeh, Behzad Baradaran
The lung tissue expresses the cholinergic system including nicotinic acetylcholine receptors (nAChRs) which included in many physiologic and pathologic processes. Mounting evidence revealed that these receptors have important roles in lung carcinogenesis via modulating either stimulatory or inhibitory signaling pathways. Among different members of nicotinic receptors family, alpha7-subtype of nAChR (α7nAChR) is a critical mediator involved in both inflammatory responses and cancers. Several studies have shown that this receptor is the most powerful regulator of responses that stimulate lung cancer processes such as proliferation, angiogenesis, metastasis, and inhibition of apoptosis...
January 30, 2019: Journal of Cellular Physiology
Covantes-Rosales Carlos Eduardo, Toledo-Ibarra Gladys Alejandra, Díaz-Resendiz Karina Janice Guadalupe, Ventura-Ramón Guadalupe Herminia, Pavón Lenin, Becerril-Villanueva Enrique, Bauer Moisés Evandro, Bottaso Oscar, Girón-Pérez Manuel Iván
The expression of elements of the cholinergic system has been demonstrated in non-neuronal cells, such as immune cells, where acetylcholine modulates innate and adaptive responses. However, the study of the non-neuronal cholinergic system has focused on lymphocyte cholinergic mechanisms, with less attention to its role of innate cells. Considering this background, the aims of this review are 1) to review information regarding the cholinergic components of innate immune system cells; 2) to discuss the effect of cholinergic stimuli on cell functions; 3) and to describe the importance of cholinergic stimuli on host immunocompetence, in order to set the base for the design of intervention strategies in the biomedical field...
January 17, 2019: Journal of Neuroimmunology
Christopher Nile, Monica Falleni, Daniela Cirasola, Abeer Alghamdi, Oliver F Anderson, Christopher Delaney, Gordon Ramage, Emerenziana Ottaviano, Delfina Tosi, Gaetano Bulfamante, Giulia Morace, Elisa Borghi
Acetylcholine modulates the virulence of Candida albicans and regulates an appropriate immune response to infection in a Galleria mellonella infection model. Indeed, the evidence suggests that C. albicans possesses a functional cholinergic receptor that can regulate filamentous growth and biofilm formation. Furthermore, G. mellonella immune cell subsets possess repertories of cholinergic receptors which regulate an effective and appropriate cellular immune response to C. albicans infection. This study aimed to investigate the cholinergic receptor subtype involved in regulation of filamentous growth and biofilm formation by C...
January 23, 2019: MSphere
Tsuyoshi Inoue, Chikara Abe, Takahide Kohro, Shinji Tanaka, Liping Huang, Junlan Yao, Shuqiu Zheng, Hong Ye, Reiko Inagi, Ruth L Stornetta, Diane L Rosin, Masaomi Nangaku, Youichiro Wada, Mark D Okusa
The cholinergic anti-inflammatory pathway (CAP) links the nervous and immune systems and modulates innate and adaptive immunity. Activation of the CAP by vagus nerve stimulation exerts protective effects in a wide variety of clinical disorders including rheumatoid arthritis and Crohn's disease, and in murine models of acute kidney injury including ischemia/reperfusion injury (IRI). The canonical CAP pathway involves activation of splenic alpha7-nicotinic acetylcholine receptor (α7nAChR)-positive macrophages by splenic β2-adrenergic receptor-positive CD4+ T cells...
January 19, 2019: Kidney International
Heli Härönen, Zarin Zainul, Nikolay Naumenko, Raija Sormunen, Ilkka Miinalainen, Anastasia Shakirzyanova, Sabrina Santoleri, Antti V Kemppainen, Rashid Giniatullin, Taina Pihlajaniemi, Anne Heikkinen
Transmembrane collagen XIII has been linked to maturation of the musculoskeletal system. Its absence in mice (Col13a1-/- ) results in impaired neuromuscular junction (NMJ) differentiation and function, while transgenic overexpression (Col13a1oe ) leads to abnormally high bone mass. Similarly, loss-of-function mutations in COL13A1 in man produce muscle weakness, decreased motor synapse function and mild dysmorphic skeletal features. Here analysis of the exogenous overexpression of collagen XIII in various muscles revealed highly increased transcript and protein levels, especially in the diaphragm...
January 22, 2019: European Journal of Neuroscience
Alina Buture, Jason W Boland, Lisa Dikomitis, Fayyaz Ahmed
Objective: Cluster headache (CH) is the most severe primary headache condition. Its pathophysiology is multifaceted and incompletely understood. This review brings together the latest neuroimaging and neuropeptide evidence on the pathophysiology of CH. Methods: A review of the literature was conducted by searching PubMed and Web of Science. The search was conducted using the following keywords: imaging studies, voxel-based morphometry, diffusion-tensor imaging, diffusion magnetic resonance imaging, tractography, connectivity, cerebral networks, neuromodulation, central modulation, deep brain stimulation, orexin-A, orexin-B, tract-based spatial statistics, single-photon emission computer tomography studies, positron-emission tomography, functional magnetic resonance imaging, magnetic resonance spectroscopy, trigeminovascular system, neuropeptides, calcitonin gene-related peptide, neurokinin A, substance P, nitric oxide synthase, pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide, neuropeptide Y, acetylcholine, noradrenaline, and ATP...
2019: Journal of Pain Research
Yuanyuan Liu, Zhongying Liu, Mengying Wei, Mingxin Hu, Kexin Yue, Rongbing Bi, Shan Zhai, Zifeng Pi, Fengrui Song, Zhiqiang Liu
Schisandra chinensis (Turcz.) Baill is produced mainly in northeast China, Korea and Japan. Its fruit has been used in food as a nutritional and functional ingredient for centuries. Polysaccharide is an important chemical component in Schisandra. Previous studies have shown that Schisandra polysaccharide (SCP) could be used to improve cognitive function clinically and treat age-related neurodegenerative disorders. In this study, a urinary metabolomics method based on ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was established to investigate the change of endogenous metabolites in an amyloid β-protein (Aβ) 25-35-induced Alzheimer's disease (AD) rat model...
January 9, 2019: Food & Function
Duncan Laverty, Rooma Desai, Tomasz Uchański, Simonas Masiulis, Wojciech J Stec, Tomas Malinauskas, Jasenko Zivanov, Els Pardon, Jan Steyaert, Keith W Miller, A Radu Aricescu
Type A γ-aminobutyric acid (GABAA ) receptors are pentameric ligand-gated ion channels and the main drivers of fast inhibitory neurotransmission in the vertebrate nervous system1,2 . Their dysfunction is implicated in a range of neurological disorders, including depression, epilepsy and schizophrenia3,4 . Among the numerous assemblies that are theoretically possible, the most prevalent in the brain are the α1β2/3γ2 GABAA receptors5 . The β3 subunit has an important role in maintaining inhibitory tone, and the expression of this subunit alone is sufficient to rescue inhibitory synaptic transmission in β1-β3 triple knockout neurons6 ...
January 2, 2019: Nature
Fumihiro Saika, Norikazu Kiguchi, Shinsuke Matsuzaki, Daichi Kobayashi, Shiroh Kishioka
Despite the requirement for effective medication against neuropathic pain associated with type 2 diabetes-mellitus (T2DM), mechanism-based pharmacotherapy has yet to be established. Given that long-lasting neuroinflammation, driven by inflammatory macrophages in the peripheral nerves, plays a pivotal role in intractable pain, it is important to determine whether inflammatory macrophages contribute to neuropathic pain associated with T2DM. To generate an experimental model of T2DM, C57BL/6J mice were fed a high-fat diet (HFD) ad libitum...
January 2, 2019: Journal of Pharmacology and Experimental Therapeutics
Takashi Nishioka, Hiroyuki Tada, Soichiro Ibaragi, Changyan Chen, Takashi Sasano
Oral cancer and smoking are closely related, because the oral cavity, which is the route of ingestion of tobacco smoke, is in direct contact with the oral mucosa. Nicotine, one of the components of tobacco, can diffuse rapidly to the central nervous system and is responsible for tobacco addiction. Nicotine is present in high concentrations in the bloodstream of smokers; while the addictive effects of this alkaloid have extensively been studied, its effect on tumorigenesis is not clear yet. Therefore, in this study, we examined the effect of nicotine on cell proliferation and the signaling pathways it activates...
February 5, 2019: Biochemical and Biophysical Research Communications
Anmin Ren, Hongxian Wu, Liping Liu, Zhenzhen Guo, Qunan Cao, Qiuyan Dai
α1 Nicotinic acetylcholine receptor (α1nAChR) is an important nicotine receptor that is widely distributed in vascular smooth muscle cells, macrophages, and endothelial cells. However, the role of α1nAChR in nicotine-mediated atherosclerosis remains unclear. The administration of nicotine for 12 weeks increased the area of the atherosclerotic lesion, the number of macrophages infiltrating the plaques, and the circulating levels of inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, in apolipoprotein E-deficient (ApoE-/- ) mice fed a high-fat diet...
December 26, 2018: Journal of Cellular Physiology
Kai-Ge Ma, Yi-Hua Qian
Alzheimer's disease (AD) is one of the major disabling and lethal diseases for aged individuals worldwide. To date, there are more than 10 hypotheses proposed for AD pathology. The beta-amyloid (Aβ) cascade hypothesis is the most widely accepted and proposes that the accumulation of Aβ in the brain is one potential mechanism for AD pathogenesis. Because some Aβ-overloaded patients do not have AD syndrome, this hypothesis is challenged from time to time. More recently, it has been shown that intracellular Aβ plays a key role in AD pathology...
December 18, 2018: Neuropeptides
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