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https://www.readbyqxmd.com/read/28800036/improved-outcomes-of-cardiopulmonary-resuscitation-in-rats-treated-with-vagus-nerve-stimulation-and-its-potential-mechanism
#1
Peng Sun, Jiangang Wang, Shen Zhao, Zhengfei Yang, Ziren Tang, Navami Ravindra, Jennifer Bradley, Joseph P Ornato, Mary Ann Peberdy, Wanchun Tang
Studies have demonstrated that vagus nerve stimulation (VNS) reduces ischemia/reperfusion (I/R) injury. In this study, we investigated the protective effects of VNS in a rat model of cardiopulmonary resuscitation (CPR). We further investigated whether the beneficial effects of VNS were dependent on the alpha 7 nicotinic acetylcholine receptor (α7nAChR). Forty animals were randomized into 4 groups and all underwent CPR (n = 10 each): (1) CPR alone (control); (2) VNS during CPR; (3) α7nAChR antagonist methyllycaconitine citrate (MLA) with VNS; (4) α7nAChR agonist 3-(2, 4-dimethoxybenzylidene) anabaseine (GTS-21) without VNS...
August 9, 2017: Shock
https://www.readbyqxmd.com/read/28797614/delayed-varenicline-administration-reduces-inflammation-and-improves-forelimb-use-following-experimental-stroke
#2
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/28797116/calcium-imaging-with-genetically-encoded-sensor-case12-facile-analysis-of-%C3%AE-7-%C3%AE-9-nachr-mutants
#3
Irina Shelukhina, Ekaterina Spirova, Denis Kudryavtsev, Lucy Ojomoko, Markus Werner, Christoph Methfessel, Michael Hollmann, Victor Tsetlin
Elucidation of the structural basis of pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs) may shed light on their involvement in different physiological functions and diseases. Combination of site-directed mutagenesis and electrophysiology is a powerful tool to pinpoint the key amino-acid residues in the receptor ligand-binding site, but for α7 and α9 nAChRs it is complicated by their poor expression and fast desensitization. Here, we probed the ligand-binding properties of α7/α9 nAChR mutants by a proposed simple and fast calcium imaging method...
2017: PloS One
https://www.readbyqxmd.com/read/28791704/granulocytes-as-models-for-human-protein-marker-identification-following-nicotine-exposure
#4
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/28791474/acetylcholine-nicotinic-receptor-subtypes-in-chromaffin-cells
#5
REVIEW
Manuel Criado
In the adrenal gland, acetylcholine released on stimulation of the sympathetic splanchnic nerve activates neuronal-type nicotinic receptors (nAChRs) in chromaffin cells and triggers catecholamine secretion. At least two subtypes of nAChRs have been described in bovine chromaffin cells. The main subtype, a heteromeric assembly of α3, β4 and perhaps α5 subunits, is involved in the activation step of the catecholamine secretion process and is not blocked by the snake toxin α-bungarotoxin. The other is α-bungarotoxin-sensitive, and its functional role has not yet been well defined...
August 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28791395/%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-inhibits-the-damage-of-rat-hippocampal-neurons-by-tlr4-myd88-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway-during-cardiopulmonary-bypass
#6
Keyan Chen, Yingjie Sun, Yugang Diao, Liu Ji, Dandan Song, Tiezheng Zhang
The present study aimed to investigate the effect of α7 nicotinic acetylcholine receptor (α7nAChR) agonist on the damage of hippocampal neurons and the expression of toll like receptor 4 (TLR4)/myeloid differentiation primary response 88 (Myd88)/nuclear factor (NF)‑κB signal pathway‑associated factors in cardiopulmonary bypass (CPB). Sprague Dawley rats were randomly divided into five groups: Sham operation (Sham); CPB; CPB + α7nAChR agonist PHA568487 (PHA); CPB + α7nAChR inhibitor MLA (MLA); and CPB + PHA568487 + TLR4 antagonist (CPT)...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28782490/unmet-needs-in-schizophrenia
#7
Maurizio Pompili, Herbert Y Meltzer
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
August 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28781257/-possible-involvement-of-neuronal-nicotinic-acetylcholine-receptors-in-compensatory-brain-mechanisms-at-early-stages-of-parkinson-s-disease
#8
E V Kryukova, I V Shelukhina, A A Kolacheva, A Kh Alieva, M I Shadrina, P A Slominsky, I E Kasheverov, Y N Utkin, M V Ugrumov, V I Tsetlin
A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson's disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative determination of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, -conotoxin MII, and -bungarotoxin as ligands. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
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
#9
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
#10
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/28776261/roles-of-na-ca-2-and-k-channels-in-the-generation-of-repetitive-firing-and-rhythmic-bursting-in-adrenal-chromaffin-cells
#11
REVIEW
Christopher J Lingle, Pedro L Martinez-Espinosa, Laura Guarina, Emilio Carbone
Adrenal chromaffin cells (CCs) are the main source of circulating catecholamines (CAs) that regulate the body response to stress. Release of CAs is controlled neurogenically by the activity of preganglionic sympathetic neurons through trains of action potentials (APs). APs in CCs are generated by robust depolarization following the activation of nicotinic and muscarinic receptors that are highly expressed in CCs. Bovine, rat, mouse, and human CCs also express a composite array of Na(+), K(+), and Ca(2+) channels that regulate the resting potential, shape the APs, and set the frequency of AP trains...
August 3, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28775316/efficient-functional-neutralization-of-lethal-peptide-toxins-in-vivo-by-oligonucleotides
#12
Tarek Mohamed Abd El-Aziz, Corinne Ravelet, Jordi Molgo, Emmanuelle Fiore, Simon Pale, Muriel Amar, Sawsan Al-Khoury, Jérôme Dejeu, Mahmoud Fadl, Michel Ronjat, Germain Sotoing Taiwe, Denis Servent, Eric Peyrin, Michel De Waard
Medical means to save the life of human patients affected by drug abuse, envenomation or critical poisoning are currently limited. While the compounds at risks are most often well identified, particularly for bioterrorism, chemical intervention to counteract the toxic effects of the ingested/injected compound(s) is restricted to the use of antibodies. Herein, we illustrate that DNA aptamers, targeted to block the pharmacophore of a poisonous compound, represent a fast-acting and reliable method of neutralization in vivo that possesses efficient and long-lasting life-saving properties...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28770361/exploring-the-binding-energy-profiles-of-full-agonists-partial-agonists-and-antagonists-of-the-%C3%AE-7-nicotinic-acetylcholine-receptor
#13
Nargis Tabassum, Qianyun Ma, Guanzhao Wu, Tao Jiang, Rilei Yu
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure...
September 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28768663/effects-of-multiple-simulated-birth-traumas-on-urethral-continence-function-in-rats
#14
Satoru Yoshikawa, Yasuhiro Sumino, Joonbeom Kwon, Takahisa Suzuki, Takeya Kitta, Minoru Miyazato, Naoki Yoshimura
Multiple vaginal parities have been reported to be an important risk factor for stress urinary incontinence (SUI). Simulated birth trauma with single vaginal distention (VD) has been used to induce the SUI condition in animals; however, the effect of multiple simulated birth traumas on the urethral continence function has not been well characterized. Therefore, we examined the effects of multiple VDs on urethral functions in vivo and the changes in gene expressions of several molecules in the urethra using female SD rats, which were divided into 3 groups; sham, VD-1 (single VD), and VD-3 groups (3 times of VDs every 2 weeks)...
August 2, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28766701/rationale-for-an-adjunctive-therapy-with-fenofibrate-in-pharmacoresistant-nocturnal-frontal-lobe-epilepsy
#15
Monica Puligheddu, Miriam Melis, Giuliano Pillolla, Giulia Milioli, Liborio Parrino, Giovanni Mario Terzano, Sonia Aroni, Claudia Sagheddu, Francesco Marrosu, Marco Pistis, Anna Lisa Muntoni
OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR...
August 2, 2017: Epilepsia
https://www.readbyqxmd.com/read/28766689/nicotine-induces-tipe2-upregulation-and-stat3-phosphorylation-contributes-to-cholinergic-anti-inflammatory-effect
#16
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/28766156/a-primer-on-nerve-agents-what-the-emergency-responder-anesthesiologist-and-intensivist-needs-to-know
#17
Keith Candiotti
PURPOSE: The purpose of this review article is to familiarize first responders, anesthesiologists, and intensivists with the medical management of patients exposed to nerve agents. SOURCE: This review is based on the current medical literature available to the general medical community. PRINCIPAL FINDINGS: Nerve agents are some of the deadliest substances known to humanity. Though they kill primarily via muscle paralysis, which leads to respiratory arrest, these agents affect virtually every organ system in the body...
August 1, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28763248/evaluating-commercially-available-antibodies-for-rat-%C3%AE-7-nicotinic-acetylcholine-receptors
#18
Brijesh K Garg, Ralph H Loring
Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) are important drug targets in neurological disorders and inflammation, making their detection and localization by validated antibodies highly desirable. However, tests in knockout animals raised questions about specificity of antibodies to mouse α7 nAChRs. To date, methods for validating antibodies for rat or human α7 nAChR have not been reported. We developed a gel-shift assay for western blots using GH4C1 cells expressing either native rat receptors or α7 nAChR-green fluorescent protein (GFP) chimeras to evaluate seven commercially available α7 nAChR antibodies...
August 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#19
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/28762161/muscarinic-receptors-in-adrenal-chromaffin-cells-physiological-role-and-regulation-of-ion-channels
#20
REVIEW
Masumi Inoue, Hidetada Matsuoka, Keita Harada, Lung-Sen Kao
Adrenal medullary chromaffin cells in mammals are innervated by sympathetic preganglionic nerve fibers, as are sympathetic ganglion neurons. Acetylcholine in the ganglion neurons is well established as mediating fast and slow excitatory postsynaptic potentials through nicotinic and muscarinic acetylcholine receptors (AChRs), respectively. The role of muscarinic AChRs during neuronal transmission in chromaffin cells varies among different mammals. Furthermore, the ion channel mechanisms associated with the muscarinic AChR-mediated increase in excitability of chromaffin cells are complicated and different from the excitation of ganglion neurons, which has been ascribed to the inhibition of M-type K(+) channels...
July 31, 2017: Pflügers Archiv: European Journal of Physiology
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