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Muscarinic receptors

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https://www.readbyqxmd.com/read/29775722/inflammatory-and-oxidative-mechanisms-potentiate-bifenthrin-induced-neurological-alterations-and-anxiety-like-behavior-in-adult-rats
#1
Brahim Gargouri, Harsharan S Bhatia, Michèle Bouchard, Bernd L Fiebich, Hamadi Fetoui
Bifenthrin (BF) is a synthetic pyrethroid pesticide widely used in several countries to manage insect pests on diverse agricultural crops. Growing evidence indicates that BF exposure is associated with an increased risk of developing neurodegenerative disorders. However, the mechanisms by which BF induces neurological and anxiety alterations in the frontal cortex and striatum are not well known. The present in vivo study was carried out to determine whether reactive oxygen species (ROS)-mediated oxidative stress (OS) and neuroinflammation are involved in such alterations...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29775673/gender-dependent-contribution-of-muscarinic-receptors-in-memory-retrieval-under-sub-chronic-stress
#2
Habiba Rashid, Touqeer Ahmed
Stress induces retrograde amnesia in humans and rodents. Muscarinic antagonism under normal physiological conditions causes gender dependent impairment in episodic memory retrieval. We aimed to explore the gender dependent role of muscarinic receptors in memory retrieval under sub-chronic stress condition. Male and female mice were trained for Morris water maze test and contextual fear conditioning, followed by 3 hour restraint stress per day for five days. Stress was either given alone or in combination with a daily subcutaneous injection of scopolamine (1 mg/kg) or donepezil (1 mg/kg)...
May 15, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29772545/autoantibodies-against-muscarinic-acetylcholine-receptor-m-3-in-sjogren-s-syndrome-and-corresponding-mouse-models
#3
Xinhua Yu, Gabriela Riemekasten, Frank Petersen
Muscarinic acetylcholine receptor M3 (M3R) is a GPCR on exocrine gland cells involved in fluid secretion. In the last two decades, evidence has been accumulated arguing for a role of autoantibodies (aab) against M3R in the development of Sjögren's syndrome (SS). In this review, we provide an updated overview on this issue and critically discuss the relation between autoimmunity to M3R and SS pathogenesis. Clinical data as well as findings from experimental disease were summarized in categories addressing the presence of aab against M3R in SS patients, the function of anti-M3R aab, the association of aab against M3R with SS-related phenotypes, in vivo pathogenicity of transferred aab against M3R in mice, and mouse models induced via immunization with M3R...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29765331/high-ph-sensitive-store-operated-ca-2-entry-mediated-by-ca-2-release-activated-ca-2-channels-in-rat-odontoblasts
#4
Maki Kimura, Koichi Nishi, Asuka Higashikawa, Sadao Ohyama, Kaoru Sakurai, Masakazu Tazaki, Yoshiyuki Shibukawa
Odontoblasts play a crucial role in dentin formation and sensory transduction following the application of stimuli to the dentin surface. Various exogenous and endogenous stimuli elicit an increase in the intracellular free calcium concentration ([Ca2+ ]i ) in odontoblasts, which is mediated by Ca2+ release from intracellular Ca2+ stores and/or Ca2+ influx from the extracellular medium. In a previous study, we demonstrated that the depletion of Ca2+ stores in odontoblasts activated store-operated Ca2+ entry (SOCE), a Ca2+ influx pathway...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29765214/tiotropium-inhibits-methacholine-induced-extracellular-matrix-production-via-%C3%AE-catenin-signaling-in-human-airway-smooth-muscle-cells
#5
Yating Huo, Lili Guan, Jiawen Xu, Luqian Zhou, Rongchang Chen
Background: Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29757584/effects-of-nerve-growth-factor-shrna-inhibition-on-asthma-phenotypes-in-a-mouse-model-of-asthma
#6
Jinhong Wu, Bing Chen, Wenxian Li, Yanan Xiao
Nerve growth factor (NGF) plays an important role in airway hyper-responsiveness (AHR). In this study, we aimed at investigating the effect of NGF inhibition on AHR and other asthma phenotypes in a mouse model of asthma. 12 mice in each group were injected with lentiviral vectors expressing non-targeting shRNA (sham shRNA), targeting NGF (shRNA-1 and shRNA-2), or normal saline for control before the asthma models were established. Peak inspiratory pressure (PIP), NGF levels in bronchoalveolar lavage fluid (BALF), and bronchoconstriction in response to acetylcholine (ACh) were measured...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29751997/modulation-of-nesfatin-1-induced-cardiovascular-effects-by-the-central-cholinergic-system
#7
Begum Aydin, Gokcen Guvenc, Burcin Altinbas, Nasir Niaz, Murat Yalcin
Nesfatin-1, a peptide whose receptor is yet to be identified, has been shown to be involved in the modulation of feeding, stress, and metabolic responses. Recently, increasing evidence has supported a modulatory role of nesfatin-1 in cardiovascular activity. We have previously reported that nesfatin-1 causes an increase in blood pressure in normotensive and hypotensive rats by increasing plasma catecholamine, vasopressin, and renin levels. Recent reports suggest that nesfatin-1 may activate the central cholinergic system...
May 4, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29751234/pyridinyl-and-pyridazinyl-3-6-diazabicyclo-3-1-1-heptane-anilines-novel-selective-ligands-with-subnanomolar-affinity-for-%C3%AE-4-%C3%AE-2-nach-receptors
#8
Francesco Deligia, Gabriele Murineddu, Cecilia Gotti, Giulio Ragusa, Francesca Fasoli, Miriam Sciaccaluga, Simona Plutino, Sergio Fucile, Giovanni Loriga, Battistina Asproni, Gerard A Pinna
The cholinergic pathways in the central nervous system (CNS) of animals and humans are important for cognitive and behavioural functions. Until a few years ago, it was thought that the key molecules transducing the cholinergic message were the metabotropic muscarinic receptors, but it is now known that ionotropic neuronal nicotinic receptors (nAChRs) are also involved. Based on recent studies, we prepared a small library of novel 3-substituted-3,6-diazabicyclo [3.1.1]heptanes, whose binding activity and functionality have been assayed...
April 17, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29742799/hippocampal-place-cell-dysfunction-and-the-effects-of-muscarinic-m-1-receptor-agonism-in-a-rat-model-of-alzheimer-s-disease
#9
Claire R Galloway, Kaushik Ravipati, Suyashi Singh, Evan P Lebois, Robert M Cohen, Allan I Levey, Joseph R Manns
Alzheimer's disease (AD) is a neurodegenerative disease that disproportionately impacts memory and the hippocampus. However, it is unclear how AD pathology influences the activity of surviving neurons in the hippocampus to contribute to the memory symptoms in AD. One well-understood connection between spatial memory and neuronal activity in healthy brains is the activity of place cells, neurons in the hippocampus that fire preferentially in a specific location of a given environment (the place field of the place cell)...
May 9, 2018: Hippocampus
https://www.readbyqxmd.com/read/29741535/amanita-muscaria-fly-agaric-from-a-shamanistic-hallucinogen-to-the-search-for-acetylcholine
#10
M R Lee, E Dukan, I Milne
The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility...
March 2018: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/29740282/muscarinic-m4-receptors-on-cholinergic-and-dopamine-d1-receptor-expressing-neurons-have-opposing-functionality-for-positive-reinforcement-and-influence-impulsivity
#11
Anna M Klawonn, Daniel B Wilhelms, Sarah H Lindström, Anand Kumar Singh, Maarit Jaarola, Jürgen Wess, Michael Fritz, David Engblom
The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29740092/bile-acids-and-their-respective-conjugates-elicit-different-responses-in-neonatal-cardiomyocytes-role-of-gi-protein-muscarinic-receptors-and-tgr5
#12
Effendi Ibrahim, Ivan Diakonov, Dulasi Arunthavarajah, Teresa Swift, Mary Goodwin, Saraid McIlvride, Vanya Nikolova, Catherine Williamson, Julia Gorelik
Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739869/synaptic-release-of-acetylcholine-rapidly-suppresses-cortical-activity-by-recruiting-muscarinic-receptors-in-layer-4
#13
Rajan Dasgupta, Frederik Seibt, Michael Beierlein
Cholinergic afferents from the basal forebrain (BF) can influence cortical activity on rapid time scales, enabling sensory information processing and exploratory behavior. However, our understanding of how synaptically released acetylcholine (ACh) influences cellular targets in distinct cortical layers remains incomplete. Previous studies have shown that rapid changes in cortical dynamics induced by phasic BF activity can be mediated by the activation of nicotinic ACh receptors (nAChRs) expressed in distinct types of GABAergic interneurons...
May 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29736245/pharmacological-properties-of-revefenacin-td-4208-a-novel-nebulized-long-acting-and-lung-selective-muscarinic-antagonist-at-human-recombinant-muscarinic-receptors-and-in-rat-guinea-pig-and-human-isolated-airway-tissues
#14
Sharath S Hegde, M Teresa Pulido-Rios, Mark A Luttmann, James J Foley, Gerald E Hunsberger, Tod Steinfeld, TaeWeon Lee, Yuhua Ji, Mathai M Mammen, Jeffrey R Jasper
Revefenacin (TD-4208) is a novel, long-acting, and lung-selective muscarinic cholinergic receptor (mAChR) antagonist in development as a nebulized inhalation solution for the treatment of chronic obstructive pulmonary disease (COPD) patients. This study evaluated the pharmacology of revefenacin at human recombinant mAChRs and in airway tissues from rats, guinea pigs, and humans. At human recombinant mAChRs, revefenacin displayed high affinity (pKI  = 8.2-9.8) and behaved as a competitive antagonist (pKI, apparent = 9...
June 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29732965/otilonium-bromide-a-drug-with-a-complex-mechanism-of-action
#15
Stefano Evangelista, Chiara Traini, Maria Giuliana Vannucchi
Otilonium bromide (OB) is a drug with spasmolytic activity belonging to quaternary ammonium derivatives and extensively used to treat patients affected by the irritable bowel syndrome (IBS). Thanks to its peculiar pharmacokinetic, OB concentrates in the large bowel wall and acts locally. From the pharmacodynamics point of view, OB is able to inhibit i) the main patterns of human colonic motility in vitro; ii) the contractility caused by excitatory motor neurons stimulation (pre-synaptic action) and iii) the contractility caused by the direct action of excitatory neurotransmitters (post-synaptic action)...
May 7, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29729357/effects-of-systemic-cholinergic-antagonism-on-reinforcer-devaluation-in-macaques
#16
Hannah F Waguespack, Ludise Málková, Patrick A Forcelli, Janita Turchi
The capacity to adjust actions based on new information is a vital cognitive function. An animal's ability to adapt behavioral responses according to changes in reward value can be measured using a reinforcer devaluation task, wherein the desirability of a given object is reduced by decreasing the value of the associated food reinforcement. Elements of the neural circuits serving this ability have been studied in both rodents and nonhuman primates. Specifically, the basolateral amygdala, orbitofrontal cortex, nucleus accumbens, and mediodorsal thalamus have each been shown to play a critical role in the process of value updating, required for adaptive goal selection...
May 2, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29723926/variation-in-cardiovascular-risk-related-to-individual-antimuscarinic-drugs-used-to-treat-overactive-bladder-a-cohort-study-in-the-uk
#17
Alejandro Arana, Andrea V Margulis, Lisa J McQuay, Ryan Ziemiecki, Jennifer L Bartsch, Kenneth J Rothman, Billy Franks, Milbhor D Silva, Kwame Appenteng, Cristina Varas-Lorenzo, Susana Perez-Gutthann
BACKGROUND: Blocking muscarinic receptors could have an effect upon cardiac function, especially among elderly patients with overactive bladder (OAB). STUDY OBJECTIVE: To investigate the risk of cardiovascular events in users of antimuscarinic drugs to treat OAB. DESIGN, SETTING AND PARTICIPANTS: Cohort study of new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium, aged ≥18 years old in the United Kingdom's Clinical Practice Research Datalink (CPRD), 2004-2012...
May 3, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29719628/novel-water-soluble-lignin-derivative-bp-cx-1-identification-of-components-and-screening-of-potential-targets-in-silico-and-in-vitro
#18
Elena I Fedoros, Alexey A Orlov, Alexander Zherebker, Ekaterina A Gubareva, Mikhail A Maydin, Andrey I Konstantinov, Konstantin A Krasnov, Ruben N Karapetian, Ekaterina I Izotova, Sergey E Pigarev, Andrey V Panchenko, Margarita L Tyndyk, Dmitry I Osolodkin, Evgeny N Nikolaev, Irina V Perminova, Vladimir N Anisimov
Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29717937/deletion-or-pharmacological-blockade-of-toll-like-receptor-4-tlr4-confers-protection-against-cyclophosphamide-induced-mouse-cystitis
#19
Mariana G de Oliveira, Fabiola Zakia Mónica, Fabiano B Calmasini, Eduardo C Alexandre, Edith B G Tavares, Antonio G Soares, Soraia K P Costa, Edson Antunes
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. We investigate the role of toll-like receptor (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. Males C57BL/6 (wild-type, WT) and/or TLR4 knockout (TLR4-/-) were treated with an injection of CYP (300 mg/kg, 24 h) or saline (10 ml/kg). The pharmacological blockade of the TLR4 by resatorvid (10 mg/kg) was also performed 1 h prior CYP-injection in WT mice...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29716863/analysis-of-the-main-constituents-of-changshu-tablet-and-its-spasmolysis-effect-against-contraction-induced-by-acetylcholine-in-the-rat-isolated-intestinal-smooth-muscle
#20
Ying An, Guangming Song, Dailin Liu, Tianyi Mao, Yanmin Zhao, Wenli Xie
The Changshu tablet (CST), one kind of Chinese patent medicine with astringent to the intestine and relieving diarrhea, was made by the root of Rose odorata Sweet var. gigantean (Coll.et Hemsl.) Rehd.et Wils. Although CST has a long history of clinical application, but the research of its chemical composition is less. So the objective of this study was to investigate the main constituents and preliminarily research its effect of the contraction of isolated intestine in vitro. The contents of total polyphenols (126...
May 2018: Pakistan Journal of Pharmaceutical Sciences
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