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Cholinergic receptor

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https://www.readbyqxmd.com/read/28818494/gts-21-reduces-microvascular-permeability-during-experimental-endotoxemia
#1
Karsten Schmidt, Sukanya Bhakdisongkhram, Florian Uhle, Christoph Philipsenburg, Aleksandar R Zivkovic, Thorsten Brenner, Johann Motsch, Markus A Weigand, Stefan Hofer
INTRODUCTION: No effective pharmacological therapy is currently available to attenuate tissue edema formation due to increased microvascular permeability in sepsis. Cholinergic mediators have been demonstrated to exert anti-inflammatory effects via the α7 nicotinic acetylcholine receptor (α7nAChR) during inflammation. GTS-21, a partial α7nAChR agonist, is an appealing therapeutic substance for sepsis-induced microvascular inflammation due to its demonstrated cholinergic anti-inflammatory properties and its favorable safety profile in clinical trials...
August 14, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28815595/sigma-1-receptor-ligands-inhibit-catecholamine-secretion-from-adrenal-chromaffin-cells-due-to-block-of-nicotinic-acetylcholine-receptors
#2
Rebecca L Brindley, Mary Beth Bauer, Nolan D Hartley, Kyle J Horning, Kevin P M Currie
Adrenal chromaffin cells (ACCs) are the neuroendocrine arm of the sympathetic nervous system and key mediators of the physiological stress response. Acetylcholine (ACh) released from preganglionic splanchnic nerves activates nicotinic acetylcholine receptors (nAChRs) on chromaffin cells causing membrane depolarization, opening voltage-gated Ca(2+) channels (VGCC), and exocytosis of catecholamines and neuropeptides. The serotonin transporter (SERT) is expressed in ACCs and interacts with 5-HT1A receptors to control secretion...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28809075/allosteric-modulation-of-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-desformylflustrabromine-potentiates-antiallodynic-response-of-nicotine-in-a-mouse-model-of-neuropathic-pain
#3
D Bagdas, D Ergun, A Jackson, W Toma, M K Schulte, M I Damaj
BACKGROUND: Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. The α4β2 subtype of nAChRs plays an important role in the mediation of pain and several nicotine-evoked responses. Agonists and partial agonists of α4β2 nAChRs show efficacy in animal pain models. In addition, the antinociceptive properties of nicotine, a non-selective nAChR agonist with a high affinity for α4β2 nAChRs, is well-known. There is a growing body of evidence pointing to allosteric modulation of nAChRs as an alternative treatment strategy in experimental pain...
August 14, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28807620/muscarinic-acetylcholine-receptor-but-not-nicotinic-acetylcholine-receptor-plays-a-role-in-morphine-induced-behavioral-sensitization-in-rats
#4
Jinling Sun, Lin Tian, Ruisi Cui, Heng Ruan, Xinwang Li
Background and Aim The cholinergic system can affect drug reward. The present study aimed to examine the roles of muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) in morphine-induced behavioral sensitization. METHODS: To analyze the roles of mAChR and nAChR in behavioral sensitization induced by morphine (5mg/kg), seven experiments were designed. Experiments 1 and 2 examined the effects of 3, 1, and 0.3 mg/kg scopolamine and 0.2, 0.1, and 0.05mg/kg scopolamine, respectively, on the locomotor activity when administered alone...
August 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28803853/developmental-suppression-of-forebrain-trka-receptors-and-attentional-capacities-in-aging-rats-a-longitudinal-study
#5
Brittney Yegla, Vinay Parikh
Basal forebrain (BF) cholinergic neurons innervating the cortex regulate cognitive, specifically attentional, processes. Cholinergic atrophy and cognitive decline occur at an accelerated pace in age-related neurodegenerative disorders such as Alzheimer's disease; however, the mechanism responsible for this phenomenon remains unknown. Here we hypothesized that developmental suppression of nerve growth factor signaling, mediated via tropomyosin-related kinase A (trkA) receptors, would escalate age-related attentional vulnerability...
August 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28799255/synergy-between-5-ht4-receptor-stimulation-and-phosphodiesterase-4-inhibition-in-facilitating-acetylcholine-release-in-human-large-intestinal-circular-muscle
#6
V Pauwelyn, W Ceelen, R A Lefebvre
BACKGROUND: Gastroprokinetic properties of 5-HT4 receptor agonists, such as prucalopride, are attributed to activation of 5-HT4 receptors on cholinergic nerves innervating smooth muscle in the gastrointestinal smooth muscle layer, increasing acetylcholine release and muscle contraction. In porcine stomach and colon, phosphodiesterase (PDE) 4 has been shown to control the signaling pathway of these 5-HT4 receptors. The aim of this study was to investigate the PDE-mediated control of these 5-HT4 receptors in human large intestine...
August 10, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28797614/delayed-varenicline-administration-reduces-inflammation-and-improves-forelimb-use-following-experimental-stroke
#7
Siyi Chen, Laura Bennet, Ailsa L McGregor
BACKGROUND: Pharmacological activation of the cholinergic anti-inflammatory pathway (CAP), specifically by activating α7 nicotinic acetylcholine receptors, has been shown to confer short-term improvements in outcome. Most studies have investigated administration within 24 hours of stroke, and few have investigated drugs approved for use in human patients. We investigated whether delayed administration of varenicline, a high-affinity agonist at α7 nicotinic receptors and an established therapy for nicotine addiction, decreased brain inflammation and improved functional performance in a mouse model of experimental stroke...
August 7, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#8
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28791704/granulocytes-as-models-for-human-protein-marker-identification-following-nicotine-exposure
#9
REVIEW
Matthew J Mulcahy, Henry A Lester
Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian CNS, in the peripheral nervous system, and in skeletal muscle. Neuronal-type nAChRs are also found in several non-neuronal cell types, including leukocytes. Granulocytes are a subtype of leukocytes that include basophils, eosinophils, and neutrophils. Granulocytes, also known as polymorphonuclear leukocytes, are characterized by their ability to produce, store, and release compounds from intracellular granules...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28780166/5-desmethylnobiletin-augments-synaptic-ach-levels-and-nicotinic-ach-receptor-activity-a-potential-candidate-for-alleviation-of-cholinergic-dysfunction
#10
Shalini Trivedi, Priyanka Maurya, Shreesh Raj Sammi, Madan Mohan Gupta, Rakesh Pandey
Cholinergic function is compromised in plethora of neurodegenerative disorders especially Alzheimer's disease. Increasing acetylcholine (ACh) levels has been the mainstay in majority of the therapeutic regimens, accepted for management of disease. The present study investigates the efficacy of 5-Desmethylnobiletin (DN), a polymethoxyflavone in augmenting cholinergic function using Caenorhabditis elegans as a model organism. The studies revealed significant elevation in cholinergic transmission mediated through increased levels of ACh and activity of nicotinic acetylcholine receptors (nAChR)...
August 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28777299/ultrafast-and-slow-cholinergic-transmission-different-involvement-of-acetylcholinesterase-molecular-forms
#11
REVIEW
Yves Dunant, Victor Gisiger
Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) Ultrafast transmission. Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief impulses (1-4 ms) at high frequencies. The collagen-tailed A12 acetylcholinesterase is concentrated in the synaptic cleft of NMJs and NEJs, were it curtails the postsynaptic response by ultrafast ACh hydrolysis...
August 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28775269/hipp-neurons-in-the-dentate-gyrus-mediate-the-cholinergic-modulation-of-background-context-memory-salience
#12
Syed Ahsan Raza, Anne Albrecht, Gürsel Çalışkan, Bettina Müller, Yunus Emre Demiray, Susann Ludewig, Susanne Meis, Nicolai Faber, Roland Hartig, Burkhart Schraven, Volkmar Lessmann, Herbert Schwegler, Oliver Stork
Cholinergic neuromodulation in the hippocampus controls the salience of background context memory acquired in the presence of elemental stimuli predicting an aversive reinforcement. With pharmacogenetic inhibition we here demonstrate that hilar perforant path-associated (HIPP) cells of the dentate gyrus mediate the devaluation of background context memory during Pavlovian fear conditioning. The salience adjustment is sensitive to reduction of hilar neuropeptide Y (NPY) expression via dominant negative CREB expression in HIPP cells and to acute blockage of NPY-Y1 receptors in the dentate gyrus during conditioning...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28766689/nicotine-induces-tipe2-upregulation-and-stat3-phosphorylation-contributes-to-cholinergic-anti-inflammatory-effect
#13
Hua Xiu Sui, Shi Zhong Ke, Dan Dan Xu, Nan Nan Lu, Yi Nan Wang, Yue Hua Zhang, Feng Guang Gao
Cholinergic anti-inflammatory pathway has therapeutic effect on inflammation-associated diseases. However, the exact mechanism of nicotine-mediated anti-inflammatory effect is still unclear. TIPE2, a new member of tumor necrosis factor-α-induced protein-8 family, is a negative regulator of immune homeostasis. However, the roles of TIPE2 in cholinergic anti-inflammatory effect are still uncertain. Here, we demonstrated that nicotine exerts its anti-inflammatory effect by TIPE2 upregulation and phosphorylated stat3 mediated the inhibition of NF-κB activation, which was supported by the following evidence: firstly, both nicotine and TIPE2 inhibit pro-inflammatory cytokine release via NF-κB inactivation...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28763302/intramuscularly-injected-neurotropin-reduced-muscular-mechanical-hyperalgesia-induced-by-repeated-cold-stress-in-rats
#14
Teruaki Nasu, Shiori Murase, Yoshiko Takeda-Uchimura, Kazue Mizumura
An extract of rabbit skin inflamed by inoculation with the vaccinia virus, neurotropin [by intravenous, oral, and intramuscular (i.m.) administration], has been used in China and Japan for the treatment of chronic pain. In this study, we investigated the analgesic mechanism of i.m. neurotropin. Rats were exposed to repeated cold stress, and muscular mechanical hyperalgesia was evaluated by measuring the withdrawal threshold of the gastrocnemius muscle using Randall-Selitto apparatus. I.m. but not subcutaneous, neurotropin dose dependently reduced the repeated cold stress-induced muscular mechanical hyperalgesia for 3 h, but it had no effect in normal rats...
July 31, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#15
Wuyi Liu, Ming D Li
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system...
August 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28759616/altered-nicotine-reward-associated-behavior-following-%C3%AE-4-nachr-subunit-deletion-in-ventral-midbrain
#16
Can Peng, Staci E Engle, Yijin Yan, Marcus M Weera, Jennifer N Berry, Matthew C Arvin, Guiqing Zhao, J Michael McIntosh, Julia A Chester, Ryan M Drenan
Nicotinic acetylcholine receptors containing α4 subunits (α4β2* nAChRs) are critical for nicotinic cholinergic transmission and the addictive action of nicotine. To identify specific activities of these receptors in the adult mouse brain, we coupled targeted deletion of α4 nAChR subunits with behavioral and and electrophysiological measures of nicotine sensitivity. A viral-mediated Cre/lox approach allowed us to delete α4 from ventral midbrain (vMB) neurons. We used two behavioral assays commonly used to assess the motivational effects of drugs of abuse: home-cage oral self-administration, and place conditioning...
2017: PloS One
https://www.readbyqxmd.com/read/28755521/antibiotic-induced-microbiota-dysbiosis-impairs-neuromuscular-function-in-juvenile-mice
#17
Valentina Caputi, Ilaria Marsilio, Viviana Filpa, Silvia Cerantola, Genny Orso, Michela Bistoletti, Nicola Paccagnella, Sara De Martin, Monica Montopoli, Stefano Dall'Acqua, Francesca Crema, Iole-Maria Di Gangi, Francesca Galuppini, Isabella Lante, Sara Bogialli, Massimo Rugge, Patrizia Debetto, Cristina Giaroni, Maria Cecilia Giron
BACKGROUND AND PURPOSE: Gut microbiota is essential for the development of the gastrointestinal system, including the enteric nervous system (ENS). Early life perturbations of gut microbiota can potentially impact neurodevelopment leading to functional bowel disorders later in life. We examined the hypothesis that gut dysbiosis impairs ENS structural and functional integrity leading to gut dysmotility in juvenile mice. EXPERIMENTAL APPROACH: To induce gut dysbiosis broad-spectrum antibiotics were administered by gavage to juvenile male C57Bl/6 mice for 14 days...
July 29, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28754351/the-alpha-7-nicotinic-acetylcholine-receptor-is-involved-in-a-direct-inhibitory-effect-of-nicotine-on-gnrh-release-in-vitro-studies
#18
Elio Messi, Federica Pimpinelli, Valentina Andrè, Chiara Rigobello, Cecilia Gotti, Roberto Maggi
The activation of nicotinic cholinergic receptors (nAChR) inhibits the reproductive axis; however, it is not clear whether nicotine may directly modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH). Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of a single class of high affinity α4β2 and α7 nAchR subtypes. The exposure of GT1-1 cells to nicotine does not modify the basal accumulation of GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion experiments and inhibits, the release of GnRH induced by prostaglandin E1 or by K(+)-induced cell depolarization; these effects were reversed by D-tubocurarine and α-bungarotoxin...
July 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28754152/cerebrospinal-fluid-kynurenine-and-kynurenic-acid-concentrations-are-associated-with-coma-duration-and-long-term-neurocognitive-impairment-in-ugandan-children-with-cerebral-malaria
#19
Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert O Opoka, Paul Bangirana, Carl M Sellgren, Ronny Wickström, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy C John
BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed...
July 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28754132/interactions-between-glycopyrronium-and-indacaterol-on-cholinergic-neurotransmission-and-contractile-response-in-bovine-trachealis
#20
Michele Baroffio, Giovanni Barisione, Vito Brusasco
BACKGROUND: Muscarinic-receptor antagonists and β-adrenoceptor agonists are used, alone or in combination, as first-line treatment for chronic obstructive pulmonary disease. Both drugs decrease airway smooth muscle tone by post-junctional mechanisms but they may have opposing effects on pre-junctional acetylcholine (ACh)-release. METHODS: We studied the effects of the muscarinic-receptor antagonist glycopyrronium (GLY), the β-adrenoceptor agonist indacaterol (IND) and their combination on electrically-induced ACh-release and contractile response in isolated bovine trachealis...
July 28, 2017: Respiratory Research
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