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https://www.readbyqxmd.com/read/29225093/effects-of-the-antidepressant-mirtazapine-and-zinc-on-nicotinic-acetylcholine-receptors
#1
Andy Hernández-Abrego, Elizabeth Vázquez-Gómez, Jesús García-Colunga
Nicotinic acetylcholine receptors (nAChRs) and zinc are associated with regulation of mood and related disorders. In addition, several antidepressants inhibit muscle and neuronal nAChRs and zinc potentiates inhibitory actions of them. Moreover, mirtazapine (a noradrenergic, serotonergic and histaminergic antidepressant) inhibits muscarinic AChRs and its effects on nAChRs are unknown. Therefore, we studied the modulation of muscle α1β1γd nAChRs expressed in oocytes and native α7-containing nAChRs in hippocampal interneurons by mirtazapine and/or zinc, using voltage-clamp techniques...
December 7, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29223599/pharmacological-intervention-and-abstinence-in-smokers-undergoing-cessation-treatment-a-psychophysiological-study
#2
Yong Cui, Jeffrey M Engelmann, Jonathan Xian, Jennifer A Minnix, Cho Y Lam, Maher Karam-Hage, Paul M Cinciripini, Jason D Robinson
As a composite concept, negative affect comprises various aversive emotional experiences, such as irritability and nervousness. It is a critical motivational factor that helps maintain smoking behavior, and contributes significantly to smoking cessation failure as a core withdrawal symptom. Prior research has indicated an important role of nicotinic mechanisms in negative affect processing. The most effective smoking cessation medication, varenicline, targets nicotinic acetylcholine receptors (nAChRs) as a partial agonist, while another first-line cessation medication, bupropion, has shown antagonistic effects on nAChRs...
December 6, 2017: International Journal of Psychophysiology
https://www.readbyqxmd.com/read/29220591/cholinergic-and-cytoprotective-signaling-cascades-mediate-the-mitigative-effect-of-erythropoietin-on-acute-radiation-syndrome
#3
Shereen Mohamed Galal, Mohamed Khairy Abdel-Rafei, Hesham Hasan
The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (rhEPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ- radiation (7 Gy; total body irradiation; TBI) at the 1st day of experimental course, then received EPO (5000 IU/kg; i.p) 24 hrs post irradiation, rats were observed for 30 days of survival analysis. Administration of EPO improved 30 days survival, alleviated TBI- induced myelosuppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of rats, while bone marrow (BM) and spleen cellularity were restored...
December 8, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29215705/activation-of-fibroblasts-by-nicotine-promotes-the-epithelial-mesenchymal-transition-and-motility-of-breast-cancer-cells
#4
Pin-Cyuan Chen, Wen-Ying Lee, Hsiang-Hsi Ling, Chia-Hsiung Cheng, Ku-Chung Chen, Cheng-Wei Lin
The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Herein, we investigated the effect and molecular mechanism of nicotine on fibroblasts and its contribution to breast cancer. We found that nicotine induced the epithelial-mesenchymal transition (EMT) of breast cancer cells and promoted activation of fibroblasts...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29213229/reflex-modification-audiometry-reveals-dual-roles-for-olivocochlear-neurotransmission
#5
Paul D Allen, Anne E Luebke
Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29212186/%C3%AE-7-nachr-mediated-fas-demethylation-contributes-to-prenatal-nicotine-exposure-induced-programmed-thymocyte-apoptosis-in-mice
#6
Han-Xiao Liu, Sha Liu, Wen Qu, Hui-Yi Yan, Xiao Wen, Ting Chen, Li-Fang Hou, Jie Ping
This study aimed to investigate the effects of prenatal nicotine exposure (PNE) on thymocyte apoptosis and postnatal immune impairments in vivo and further explore the epigenetic mechanisms of the pro-apoptotic effect of nicotine in vitro. The results showed that PNE caused immune impairments in offspring on postnatal day 49, manifested as increased IL-4 production and an increased IgG1/IgG2a ratio in serum. Enhanced apoptosis of total and CD4+SP thymocytes was observed both in fetus and in offspring. Further, by exposing thymocytes to 0-100 μM of nicotine in vitro for 48 h, we found that nicotine increased α7 nicotinic acetylcholine receptor (nAChR) expression, activated the Fas apoptotic pathway, and promoted thymocyte apoptosis in concentration-dependent manners...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209071/inhaled-nicotine-equivalent-to-cigarette-smoking-disrupts-systemic-and-uterine-hemodynamics-and-induces-cardiac-arrhythmia-in-pregnant-rats
#7
Xuesi M Shao, Héctor E López-Valdés, Jing Liang, Jack L Feldman
Maternal smoking with obligatory nicotine inhalation is associated with preterm delivery, low birth weight, fetal growth retardation and developmental defects. We tested the hypothesis that cigarette smoking-relevant nicotine inhalation during pregnancy impairs cardiovascular function and uterine hemodynamics with consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine via a novel lung alveolar region-targeted aerosol method produced nicotine pharmacokinetics resembling cigarette smoking in humans...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29206881/deletion-of-lynx1-reduces-the-function-of-%C3%AE-6-nicotinic-receptors
#8
Rell L Parker, Heidi C O'Neill, Beverley M Henley, Charles R Wageman, Ryan M Drenan, Michael J Marks, Julie M Miwa, Sharon R Grady, Henry A Lester
The α6 nicotinic acetylcholine receptor (nAChR) subunit is an attractive drug target for treating nicotine addiction because it is present at limited sites in the brain including the reward pathway. Lynx1 modulates several nAChR subtypes; lynx1-nAChR interaction sites could possibly provide drug targets. We found that dopaminergic cells from the substantia nigra pars compacta (SNc) express lynx1 mRNA transcripts and, as assessed by co-immunoprecipitation, α6 receptors form stable complexes with lynx1 protein, although co-transfection with lynx1 did not affect nicotine-induced currents from cell lines transfected with α6 and β2...
2017: PloS One
https://www.readbyqxmd.com/read/29200999/confirming-a-role-for-%C3%AE-9nachrs-and-sk-potassium-channels-in-type-ii-hair-cells-of-the-turtle-posterior-crista
#9
Xiaorong Xu Parks, Donatella Contini, Paivi M Jordan, Joseph C Holt
In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs) synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh) at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29199094/%C3%AE-conotoxins-to-explore-the-molecular-physiological-and-pathophysiological-functions-of-neuronal-nicotinic-acetylcholine-receptors
#10
REVIEW
Julien Giribaldi, Sébastien Dutertre
The vast diversity of neuronal nicotinic acetylcholine subunits expressed in the central and peripheral nervous systems, as well as in non-neuronal tissues, constitutes a formidable challenge for researchers and clinicians to decipher the role of particular subtypes, including complex subunit associations, in physiological and pathophysiological functions. Many natural products target the nAChRs, but there is no richer source of nicotinic ligands than the venom of predatory gastropods known as cone snails. Indeed, every single species of cone snail was shown to produce at least one type of such α-conotoxins...
November 30, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29196961/%C3%AE-7-nachr-activation-has-an-opposite-effect-on-healing-of-covered-and-uncovered-wounds
#11
Jiao-Yong Li, Shu-Kun Jiang, Lin-Lin Wang, Meng-Zhou Zhang, Shuai Wang, Zhen-Fei Jiang, Yu-Li Liu, Hao Cheng, Miao Zhang, Rui Zhao, Da-Wei Guan
The α7 nicotinic acetylcholine receptor (α7-nAChR) is associated with inflammation, re-epithelialization, and angiogenesis in wound healing process. A recent study demonstrated that PNU-282987, a selective agonist of α7-nAChR, accelerates the repair of diabetic excisional wounds. Whether α7-nAChR activation promotes non-diabetic wounds healing is unknown. The aim of this study was to evaluate the effects of α7-nAChR activation on non-diabetic wound healing. The effects were evaluated in two wound models...
December 1, 2017: Inflammation
https://www.readbyqxmd.com/read/29196725/pharmacogenetic-study-of-seven-polymorphisms-in-three-nicotinic-acetylcholine-receptor-subunits-in-smoking-cessation-therapies
#12
Giulia Pintarelli, Antonella Galvan, Paolo Pozzi, Sara Noci, Giovanna Pasetti, Francesca Sala, Ugo Pastorino, Roberto Boffi, Francesca Colombo
Smoking-cessation therapy reduces the risk of smoking-related diseases, but is successful only in a fraction of smokers. There is growing evidence that genetic variations in nicotinic acetylcholine receptor (nAChR) subunits influence the risk of nicotine dependence and the ability to quit smoking. To investigate the role of polymorphisms in nAChR genes on smoking quantity and the outcome of smoking-cessation therapies, we carried out an association study on 337 smokers who underwent pharmacotherapy with varenicline, bupropion, nicotine replacement therapy (NRT) alone, or NRT plus bupropion...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196491/diversity-of-nicotinic-acetylcholine-receptor-positive-allosteric-modulators-revealed-by-mutagenesis-and-a-revised-structural-model
#13
Joseph Newcombe, Anna Chatzidaki, Tom D Sheppard, Maya Topf, Neil S Millar
By combining electrophysiological and computational approaches we have examined a series of positive allosteric modulators (PAMs) acting on the human α7 nicotinic acetylcholine receptor (nAChR). Electrophysiological studies have focussed on three α7-selective PAMs (A-867744, TBS-516 and TQS) that display similar effects on wild-type α7 nAChRs. In addition to potentiating agonist-evoked responses, all three compounds reduce receptor desensitisation and, consequently, are classed as type II PAMs. Despite having similar effects on wild-type receptors, A-867744 was found to have profoundly differing effects to TBS-516 and TQS on mutated receptors, a finding that is consistent with previous studies indicating that A-867744 may have a different mechanism of action to other α7-selective type II PAMs...
December 1, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29195920/loss-of-lypd6-leads-to-reduced-anxiety-like-behaviour-and-enhanced-responses-to-nicotine
#14
Maria Arvaniti, Filip S Polli, Kristi A Kohlmeier, Morten S Thomsen, Jesper T Andreasen
Nicotine consumption through smoking affects anxious states in humans. However, the precise role of nicotinic acetylcholine receptor (nAChR) circuitry in the regulation of anxiety remains elusive. The Lynx protein Lypd6 is highly enriched in synaptic loci and has been previously identified as an endogenous inhibitor of neuronal nAChR function in vitro. Here, we investigate the effect of Lypd6 in anxiety-related behaviour and examine the molecular underpinnings of its function in the brain. We employ the marble burying (MB) and elevated zero maze (EZM) tests in Lypd6 knock-out (KO) and wild-type (WT) mice and find that loss of Lypd6 leads to decreased digging behaviour in the MB test and increased time spent in the open area in the EZM test...
November 28, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29193059/exercise-improves-nicotine-reward-associated-cognitive-behaviors-and-related-%C3%AE-7-nachr-mediated-signal-transduction-in-adolescent-rats
#15
Yuehui Zhou, Cuicui Li, Rena Li, Chenglin Zhou
The adolescent brain is vulnerable to long-lasting cognitive disturbances resulting from nicotine exposure. Although exercise has been used as an intervention for ameliorating cognitive deficits in various disorders, the effect on cognitive changes induced by nicotine exposure and its underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of exercise on nicotine reward-associated cognitive behaviors in adolescent rats subjected to nicotine conditioned place preference paradigm (CPP)...
November 29, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29192197/interaction-of-synthetic-human-slurp-1-with-the-nicotinic-acetylcholine-receptors
#16
Thomas Durek, Irina V Shelukhina, Han-Shen Tae, Panumart Thongyoo, Ekaterina N Spirova, Denis S Kudryavtsev, Igor E Kasheverov, Grazyna Faure, Pierre-Jean Corringer, David J Craik, David J Adams, Victor I Tsetlin
Human SLURP-1 is a secreted protein of the Ly6/uPAR/three-finger neurotoxin family that co-localizes with nicotinic acetylcholine receptors (nAChRs) and modulates their functions. Conflicting biological activities of SLURP-1 at various nAChR subtypes have been based on heterologously produced SLURP-1 containing N- and/or C-terminal extensions. Here, we report the chemical synthesis of the 81 amino acid residue human SLURP-1 protein, characterization of its 3D structure by NMR, and its biological activity at nAChR subtypes...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29191791/electrophysiological-investigation-of-the-effect-of-structurally-different-bispyridinium-non-oxime-compounds-on-human-%C3%AE-7-nicotinic-acetylcholine-receptor-activity-an-in-vitro-structure-activity-analysis
#17
Corinna Scheffel, Karin V Niessen, Sebastian Rappenglück, Klaus T Wanner, Horst Thiermann, Franz Worek, Thomas Seeger
Organophosphorus compounds, including nerve agents and pesticides, exert their toxicity through irreversible inhibition of acetylcholinesterase (AChE) resulting in an accumulation of acetylcholine and functional impairment of muscarinic and nicotinic acetylcholine receptors. Current therapy comprises oximes to reactivate AChE and atropine to antagonize effects induced by muscarinic acetylcholine receptors. Nicotinic malfunction leading to depression of the central and peripheral respiratory system is not directly treated calling for alternative therapeutic interventions...
November 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29185480/initial-cross-over-test-of-a-positive-allosteric-modulator-of-alpha-7-nicotinic-receptors-to-aid-cessation-in-smokers-with-or-without-schizophrenia
#18
Kenneth A Perkins, Kn Roy Chengappa, Joshua L Karelitz, Margaret C Boldry, Valerie Michael, Taylor Herb, Jessica Gannon, Jaspreet Brar, Lisa Ford, Stephanie Rassnick, Darlene Brunzell
Preclinical research shows that compounds acting at α7 nicotinic receptors (nAChRs) can reduce nicotine self-administration, suggesting that a positive allosteric modulator (PAM) of α7 receptors, JNJ-39393406, may aid smoking cessation. Moreover, individuals with schizophrenia, who have very high rates of smoking, have reduced expression of α7 nAChRs and may particularly benefit from this compound. In two parallel studies using a within-subject crossover design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2), both groups high in quit interest, attempted to initiate quitting temporarily during each of two 3-week phases...
November 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29185370/effect-of-nicotine-on-placental-ischemia-induced-complement-activation-and-hypertension-in-the-rat
#19
Connor F Laule, Cameron R Wing, Evan J Odean, Jacob A Wilcox, Jeffrey S Gilbert, Jean F Regal
Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia. Nicotine, a major component of cigarettes, stimulates the efferent cholinergic anti-inflammatory pathway through peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to attenuate ischemia-reperfusion injury in kidney and liver...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29184265/long-term-low-intensity-endurance-exercise-along-with-blood-flow-restriction-improves-muscle-mass-and-neuromuscular-junction-compartments-in-old-rats
#20
Mohammad-Ali Bahreini Pour, Siyavash Joukar, Fariborz Hovanloo, Hamid Najafipour
Background: During the aging process, muscle atrophy and neuromuscular junction remodeling are inevitable. The present study aimed to clarify whether low-intensity aerobic exercise along with limb blood-flow restriction (BFR) could improve aging-induced muscle atrophy and nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. Methods: Forty-eight male Wistar rats, aged 23-24 months, were randomly divided into control, sham (Sh: subjected to surgery without BFR), BFR (subjected to BFR), exercise (Ex: subjected to 10 weeks of low-intensity exercise), Sh+Ex, and BFR+Ex groups...
November 2017: Iranian Journal of Medical Sciences
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