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Muscarinic receptors

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https://www.readbyqxmd.com/read/28091727/intrinsic-cardiac-ganglia-and-acetylcholine-are-important-in-the-mechanism-of-ischaemic-preconditioning
#1
J M J Pickard, N Burke, S M Davidson, D M Yellon
This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia-reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28091608/binding-of-n-methylscopolamine-to-the-extracellular-domain-of-muscarinic-acetylcholine-receptors
#2
Jan Jakubík, Alena Randáková, Pavel Zimčík, Esam E El-Fakahany, Vladimír Doležal
Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090742/a-novel-scale-linking-potency-and-dosage-to-estimate-anticholinergic-exposure-in-older-adults-the-muscarinic-acetylcholinergic-receptor-antagonist-exposure-scale
#3
Therese T Klamer, Maarten Wauters, Majda Azermai, Carlos Durán, Thierry Christiaens, Monique Elseviers, Robert Vander Stichele
Quantification of the anticholinergic exposure insufficiently or imprecisely incorporates dosage information, leading to inaccurate estimations. The aim was to construct a novel scale, including potency and dosage for the quantification of the anticholinergic exposure in older adults. Potency information was retrieved from a previous systematic review. The dosage range for each drug was delineated in minimal, maintenance and maximal dosage for adults and older adults. Dosage information was collected from authoritative sources and reviewed in an expert panel...
November 7, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28089847/the-binding-orientation-of-epibatidine-at-%C3%AE-7-nach-receptors
#4
Andrew J Thompson, Simon Metzger, Martin Lochner, Marc-David Ruepp
Epibatidine is an alkaloid toxin that binds with high affinity to nicotinic and muscarinic acetylcholine receptors, and has been extensively used as a research tool. To examine binding interactions at the nicotinic receptor, it has been co-crystallised with the structural homologue acetylcholine binding protein (AChBP; PDB ID 2BYQ), and with an AChBP chimaera (3SQ6) that shares 64% sequence identity with the α7 nACh receptor. However, the binding orientations revealed by AChBP co-crystal structures may not precisely represent their receptor homologues and experimental evidence is needed to verify the ligand poses...
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28089115/correlation-of-antimuscarinic-acetylcholine-receptor-antibody-titers-and-antidesmoglein-antibody-titers-with-the-severity-of-disease-in-patients-with-pemphigus
#5
Manimegalai Jeyasekaran Dhanabhakya Lakshmi, Telanseri Jaykar Jaisankar, Medha Rajappa, Devinder Mohan Thappa, Laxmisha Chandrashekar, Dakshinamurthy Divyapriya, Malathi Munisamy, Gunaseelan Revathy
BACKGROUND: Acetylcholine receptor (AchR) antibody levels significantly correlate with disease severity at initial pemphigus diagnosis and during follow-up. However, it is not clear if they are just an epiphenomenon or a potential trigger of the known pathogenic process in pemphigus vulgaris. OBJECTIVE: We sought to assess the changes in anti-muscarinic (M3) AchR and anti-desmoglein (Dsg) antibody titers with therapy. METHODS: This was a hospital-based cohort study involving 45 patients with active pemphigus...
January 11, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28078480/muscarinic-acetylcholine-receptor-mediated-tight-junction-opening-is-involved-in-epiphora-in-late-phase-of-submandibular-gland-transplantation
#6
Ning-Yan Yang, Chong Ding, Jing Li, Yan Zhang, Ruo-Lan Xiang, Li-Ling Wu, Guang-Yan Yu, Xin Cong
Submandibular gland (SMG) autotransplantation is an effective therapy for treating severe dry eye syndrome. However, epiphora occurs in more than 40% of patients 6 months after operation. We previously found that muscarinic acetylcholine receptor (mAChR) plays a crucial role in regulating SMG secretion partially through the modulation on tight junction (TJ)-based paracellular pathway. Therefore, the present study aimed to investigate the possible involvement of mAChR and TJ in a rabbit long-term model of SMG transplantation...
January 11, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28072454/non-neuronal-acetylcholine-involved-in-reproduction-in-mammals-and-honeybees
#7
REVIEW
Ignaz Wessler, Charles James Kirkpatrick
Bacteria and archaea synthesize acetylcholine (ACh). Thus it can be postulated that ACh was created by nature roughly 3 billion years ago. Therefore, the wide expression of ACh in nature (i.e. in bacteria, archaea, unicellular organisms, plants, fungi, non-vertebrates and vertebrates and the abundance of non-neuronal cells of mammals) is not surprising. The term non-neuronal ACh and non-neuronal cholinergic system have been introduced to describe the auto- and paracrine, i.e. local regulatory actions of cells not innervated by neuronal cholinergic fibers to communicate among themselves...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28070660/treatment-options-for-hyperemesis-gravidarum
#8
REVIEW
Amy Abramowitz, Emily S Miller, Katherine L Wisner
Hyperemesis gravidarum (HG) is a severe and prolonged form of nausea and/or vomiting during pregnancy. HG affects 0.3-2% of pregnancies and is defined by dehydration, ketonuria, and more than 5% body weight loss. Initial pharmacologic treatment for HG includes a combination of doxylamine and pyridoxine. Additional interventions include ondansetron or dopamine antagonists such as metoclopramide or promethazine. The options are limited for women who are not adequately treated with these medications. We suggest that mirtazapine is a useful drug in this context and its efficacy has been described in case studies...
January 9, 2017: Archives of Women's Mental Health
https://www.readbyqxmd.com/read/28069927/impact-of-altered-cholinergic-tones-on-the-neurovascular-coupling-response-to-whisker-stimulation
#9
Clotilde Lecrux, Claire H Sandoe, Sujaya Neupane, Pascal Kropf, Xavier Toussay, Xin-Kang Tong, María Lacalle-Aurioles, Amir Shmuel, Edith Hamel
Brain imaging techniques that use vascular signals to map changes in neuronal activity rely on the coupling between electrophysiology and hemodynamics, a phenomenon referred to "neurovascular coupling" (NVC). It is unknown whether this relationship remains reliable under altered brain states associated to acetylcholine (ACh) levels, such as attention and arousal, and in pathological conditions like Alzheimer's disease. We therefore assessed the effects of varying ACh tone on whisker evoked-NVC responses in rat barrel cortex, measured by cerebral blood flow (CBF) and neurophysiological recordings (local field potentials, LFPs)...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069458/loganin-enhances-long-term-potentiation-and-recovers-scopolamine-induced-learning-and-memory-impairments
#10
Eun-Sang Hwang, Hyun-Bum Kim, Seok Lee, Min-Ji Kim, Sung-Ok Lee, Seung-Moo Han, Sungho Maeng, Ji-Ho Park
Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied. Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinaliset Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine...
January 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28066150/calcium-permeability-of-transient-receptor-potential-canonical-trpc-4-channels-measured-by-trpc4-gcamp6s
#11
Juyeon Ko, Jongyun Myeong, Dongki Yang, Insuk So
Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. A TRPC4 specific activator, (-)-englerin A, induced both current and calcium fluorescence with the similar time course...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28066149/neuroprotective-effect-of-lithium-after-pilocarpine-induced-status-epilepticus-in-mice
#12
Namgue Hong, Yun-Sik Choi, Seong Yun Kim, Hee Jung Kim
Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28065942/neuregulin-1-erbb-module-in-c-bouton-synapses-on-somatic-motor-neurons-molecular-compartmentation-and-response-to-peripheral-nerve-injury
#13
Anna Casanovas, Sara Salvany, Víctor Lahoz, Olga Tarabal, Lídia Piedrafita, Raimundo Sabater, Sara Hernández, Jordi Calderó, Josep E Esquerda
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057070/distinct-pattern-of-enteric-phospho-alpha-synuclein-aggregates-and-gene-expression-profiles-in-patients-with-parkinson-s-disease
#14
Martina Barrenschee, Dimitri Zorenkov, Martina Böttner, Christina Lange, François Cossais, Amelie Bernadette Scharf, Günther Deuschl, Susanne A Schneider, Mark Ellrichmann, Annette Fritscher-Ravens, Thilo Wedel
Phosphorylated alpha-synuclein (p-α-syn) containing Lewy bodies (LBs) and Lewy neurites (LNs) are neuropathological hallmarks of Parkinson's disease (PD) in the central nervous system (CNS). Since they have been also demonstrated in the enteric nervous system (ENS) of PD patients, the aim of the study was to analyze enteric p-α-syn positive aggregates and intestinal gene expression. Submucosal rectal biopsies were obtained from patients with PD and controls and processed for dual-label-immunohistochemistry for p-α-syn and PGP 9...
January 5, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28054012/localization-of-muscarinic-acetylcholine-receptor-2-to-the-intestinal-crypt-stem-cell-compartment
#15
Eleanor D Muise, Neeru Gandotra, John J Tackett, Michaela C Bamdad, Robert A Cowles
The data presented in this article are related to the research article entitled "Distribution of muscarinic acetylcholine receptor subtypes in the murine small intestine" (E.D. Muise, N. Gandotra, J.J. Tackett, M.C. Bamdad, R.A. Cowles, 2016) [1]. We recently demonstrated that neuronal serotonin stimulates intestinal crypt cell division, and induces villus growth and crypt depth (E.R. Gross, M.D. Gershon, K.G. Margolis, Z.V. Gertsberg, Z. Li, R.A. Cowles, 2012; M.D. Gershon, 2013) [2], [3]. Scopolamine, a nonspecific muscarinic receptor antagonist, inhibited serotonin-induced intestinal mucosal growth [2]...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28053518/initiation-of-triple-therapy-maintenance-treatment-among-patients-with-copd-in-the-us
#16
Jason C Simeone, Rakesh Luthra, Shuchita Kaila, Xiaoyun Pan, Tarun D Bhagnani, Jieruo Liu, Teresa K Wilcox
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28051147/%C3%AE-2-adrenoreceptor-inverse-agonist-down-regulates-muscarine-cholinergic-subtype-3-receptor-and-its-downstream-signal-pathways-in-airway-smooth-muscle-cells-in-vitro
#17
Jian Luo, Yuan-Hua Liu, Wei Luo, Zhu Luo, Chun-Tao Liu
Mechanisms underlying β2-adrenoreceptor (β2AR) inverse agonist mediated bronchoprotectiveness remain unknown. We incubated ICI118,551, formoterol, budesonide, and formoterol plus budesonide, as well as ICI118,551 or pindolol plus formoterol, ICI118,551 plus forskolin, SQ22,536 or H89 plus formoterol in ASMCs to detect expressions of M3R, PLCβ1 and IP3. The level of M3R in the presence of 10(-5) mmol/L ICI118,551 were significantly decreased at 12 h, 24 h and 48 h (P < 0.05), and at 24 h were significantly reduced in ICI118,551 with concentration of 10(-5 )mmol/L, 10(-6 )mmol/L, 10(-7 )mmol/L, and 10(-8 )mmol/L (P < 0...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049095/riluzole-ameliorates-learning-and-memory-deficits-in-a%C3%AE-25-35-induced-rat-model-of-alzheimer-s-disease-and-is-independent-of-cholinoceptor-activation
#18
Zahra Mokhtari, Tourandokht Baluchnejadmojarad, Farnaz Nikbakht, Monireh Mansouri, Mehrdad Roghani
Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ25-35-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28049018/transactivation-of-the-epidermal-growth-factor-receptor-in-responses-to-myocardial-stress-and-cardioprotection
#19
REVIEW
Melissa E Reichelt, Shannon O'Brien, Walter G Thomas, John P Headrick
The epidermal growth factor receptor (EGFR) family comprises the ErbB1 (EGFR) and ErbB4 receptors as well as the 'co-receptors' ErbB2 (which does not bind EGF ligands) and ErbB3 (which lack tyrosine kinase activity). This family of receptors is essential for cardiac development, myocardial, renal and vascular function, and cardiac responses to physiological and pathological perturbations. The EGFR appears critical in protecting cardiac cells from injury, while considerable attention has focussed on neuregulin/ErbB4 signalling in potentially ameliorating cardiomyopathy/heart failure...
December 31, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28044440/ethylatropine-bromide-as-a-peripherally-restricted-muscarinic-antagonist
#20
Asheebo Rojas, Thota Ganesh, Alec Walker, Raymond Dingledine
Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent of these quaternary derivatives; however, it is expensive and produced in limited quantity. Here, we propose the use of ethylatropine bromide as an alternative to methylatropine. The synthesis of ethylatropine bromide is simple, inexpensive and has low environmental impact...
January 6, 2017: ACS Chemical Neuroscience
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