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https://www.readbyqxmd.com/read/29428175/beyond-the-channel-metabotropic-signaling-by-nicotinic-receptors
#1
REVIEW
Nadine Kabbani, Robert A Nichols
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel (LGIC) that plays an important role in cellular calcium signaling and contributes to several neurological diseases. Agonist binding to the α7 nAChR induces fast channel activation followed by inactivation and prolonged desensitization while triggering long-lasting calcium signaling. These activities foster neurotransmitter release, synaptic plasticity, and somatodendritic regulation in the brain. We discuss here the ability of α7 nAChRs to operate in ionotropic (α7 i ) and metabotropic (α7 m ) modes, leading to calcium-induced calcium release (CICR) and G protein-associated inositol trisphosphate (IP 3 )-induced calcium release (IICR), respectively...
February 7, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29427655/nicotinic-acetylcholine-receptors-are-associated-with-ketamine-induced-neuronal-apoptosis-in-the-developing-rat-retina
#2
Lingqi Gao, Junde Han, Jie Bai, Jing Dong, Sen Zhang, Mazhong Zhang, Jijian Zheng
Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development...
February 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29426250/%C3%AE-conotoxin-imi-modified-polymeric-micelles-as-potential-nanocarriers-for-targeted-docetaxel-delivery-to-%C3%AE-7-nachr-overexpressed-non-small-cell-lung-cancer
#3
Dong Mei, Libo Zhao, Binlong Chen, Xiaoyan Zhang, Xiaoling Wang, Zhiying Yu, Xin Ni, Qiang Zhang
A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29423839/molecular-neuronal-and-behavioral-effects-of-ethanol-and-nicotine-interactions
#4
Paul M Klenowski, Andrew R Tapper
Ethanol and nicotine can modulate the activity of several neurotransmitter systems and signalling pathways. Interactions between ethanol and nicotine can also occur via common molecular targets including nicotinic acetylcholine receptors (nAChRs). These effects can induce molecular and synaptic adaptations that over time, are consolidated in brain circuits that reinforce drug-seeking behavior, contribute to the development of withdrawal symptoms during abstinence and increase the susceptibility to relapse. This chapter will discuss the acute and chronic effects of ethanol and nicotine within the mesolimbic reward pathway and brain circuits involved in learning, memory, and withdrawal...
February 9, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29413432/effects-of-nicotine-containing-and-nicotine-free-e-cigarette-refill-liquids-on-intracranial-self-stimulation-in-rats
#5
Andrew C Harris, Peter Muelken, John R Smethells, Katrina Yershova, Irina Stepanov, Thao Tran Olson, Kenneth J Kellar, Mark G LeSage
BACKGROUND: Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids...
February 1, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29405451/nicotinic-activity-layer-specifically-modulates-synaptic-potentiation-in-the-mouse-insular-cortex
#6
Hiroki Toyoda
Nicotinic acetylcholine receptors (nAChRs) in the insular cortex play an important role in nicotine addiction, but its cellular and synaptic mechanisms underlying nicotine addiction still remain unresolved. In layer 5 pyramidal neurons of the mouse insular cortex, activation of nAChRs suppresses synaptic potentiation through enhancing GABAergic synaptic transmission via activation of β2-containing nAChRs in non-fast-spiking (non-FS) interneurons. However, it has not been addressed whether and how activation of nAChRs modulates synaptic plasticity in layer 3 and 6 pyramidal neurons of the insular cortex...
February 6, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29401517/role-of-%C3%AE-7nachr-nmdar-in-sevoflurane-induced-memory-deficits-in-the-developing-rat-hippocampus
#7
XiaoHong Tang, YiZe Li, JiYing Ao, Ling Ding, Yang Liu, Yuan Yuan, ZhiFen Wang, GuoLin Wang
Detrimental effects of volatile anaesthetics, including sevoflurane, on the structure and function of the developing brain have been reported. The internalization of N-methyl-D-aspartate receptors (NMDARs) contributes to anaesthetic neurotoxicity. Both nicotinic acetylcholine receptors (nAChRs) and NMDAR play a critical role in the development of the nervous system. Moreover, nAChR can interact with NMDAR, and previous studies have demonstrated modulation of NMDAR by nAChR. In our study, we used an α7 nicotinic acetylcholine receptor (α7nAChR) agonist and α7nAChR antagonist to explore the role of α7nAChR and NMDAR in sevoflurane-induced long-term effects on memory and dendritic spine both in vivo and in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29399064/venom-based-neural-modulators
#8
Jiao Chen, Xiao-Ming Liu, Yuan Zhang
Different types of neuronal nicotinic acetylcholine receptors (nAChRs) are expected to occur in vivo, most structure-activity relationship studies have been carried out for just a few neuronal subtypes. The present review enlightens current aspects of venom modulators of nAChRs. Important electronic databases such as PubMed or Google scholar were explored for the collection of latest studies in the field. Clinical and basic research has shown that cholinergic receptors play a role in several disorders of the nervous system such as chronic pain, Alzheimers disease and addiction to nicotine, alcohol and drugs...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29396474/nicotine-associated-breast-cancer-in-smokers-is-mediated-through-high-level-of-ezh2-expression-which-can-be-reversed-by-methyltransferase-inhibitor-dznepa
#9
Kanchan Kumari, Biswajit Das, Amit Adhya, Sanjib Chaudhary, Shantibhusan Senapati, Sandip K Mishra
Recent studies show substantial growth-promoting properties of nicotine (NIC) in cancer, which is a combined outcome of genetic and epigenetic alterations. However, the role of epigenetic modifiers in response to NIC in breast cancer is less studied. In the present study, for the first time we have shown NIC-induced enhanced EZH2 expression. Six pairs of smoking-associated breast cancer patient tissues were analyzed. Samples from smoking breast cancer patients showed distinguished enhanced EZH2 expression in comparison to non-smoking ones...
February 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29395323/%C3%AE-7-nicotinic-acetylcholine-receptors-are-involved-in-suppression-of-the-antibody-immune-response
#10
Lyudmyla Koval, Olena Kalashnyk, Olena Lykhmus, Maryna Skok
This study demonstrates that α7 nicotinic acetylcholine receptors (nAChRs) regulate mouse B lymphocyte proliferation and IgM production in ion-independent manner. The high α7 nAChR levels were found in CD5+ and Foxp3+ B cells; induction of Foxp3+ cells in vitro was attenuated in the absence or upon inhibition of α7 nAChRs. The adoptively transferred B lymphocytes, stimulated in presence of methyllicaconitine, decreased the IgM response and abolished the IgG response in the host. The data obtained demonstrate the importance of cholinergic regulation for the antibody immune response and immunosuppression...
January 30, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29384668/dual-nicotinic-acetylcholine-receptors-%C3%AE-4%C3%AE-2-antagonists-%C3%AE-7-agonists-synthesis-docking-studies-and-pharmacological-evaluation-of-tetrahydroisoquinolines-and-tetrahydroisoquinolinium-salts
#11
François Crestey, Anders A Jensen, Christian Soerensen, Charlotte Busk Magnus, Jesper T Andreasen, Günther H J Peters, Jesper L Kristensen
We describe the synthesis of tetrahydroisoquinolines and tetrahydroisoquinolinium salts together with their pharmacological properties at various nicotinic acetylcholine receptors. In general the compounds were α4β2 nAChR antagonists, with the tetrahydroisoquinolinium salts being more portent than the parent tetrahydroisoquinoline derivatives. The most potent α4β2 antagonist 6c, exhibited submicromolar binding Ki and functional IC50 values and high selectivity for this receptor over the α4β4 and α3β4 nAChRs...
January 31, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29383396/differential-effects-of-%C3%AE-4%C3%AE-2-nicotinic-receptor-antagonists-and-partial-agonists-on-contextual-fear-extinction-in-male-c57bl-6-mice
#12
Munir Gunes Kutlu, Jessica M Tumolo, Courtney Cann, Thomas J Gould
RATIONALE: Numerous studies have attributed the psychopathology of post-traumatic stress disorder (PTSD) to maladaptive behavioral responses such as an inability to extinguish fear. While exposure therapies are mostly effective in treating these disorders by enhancing extinction learning, relapse of PTSD symptoms is common. Although several studies indicated a role for cholinergic transmission and nicotinic acetylcholine receptors (nAChRs) in anxiety and stress disorder symptomatology, very little is known about the specific contribution of nAChRs to fear extinction OBJECTIVES: In the present study, we examined the effects of inhibition and desensitization of α4β2 nAChRs via a full antagonist (Dihydro-beta-erythroidine (DhβE)) and two α4β2 nAChR partial-agonists (varenicline and sazetidine-A) on contextual fear extinction, locomotor activity, and spontaneous recovery of contextual fear in mice...
January 30, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29382698/concatenated-nicotinic-acetylcholine-receptors-a-gift-or-a-curse
#13
Philip Kiær Ahring, Vivian Wan Yu Liao, Thomas Balle
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are vital for normal mammalian brain function. Cys-loop receptors are pentameric ligand-gated ion channels formed from five identical or homologous subunits oriented around a central ion-conducting pore, which result in homomeric or heteromeric receptors, respectively. Within a given Cys-loop receptor family, many different heteromeric receptors can assemble from a common set of subunits, and understanding the properties of these heteromeric receptors is crucial for the continuing quest to generate novel treatments for human diseases...
January 30, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29379089/the-alpha7-nicotinic-receptor-contributes-to-gp120-induced-neurotoxicity-implications-in-hiv-associated-neurocognitive-disorders
#14
Coral M Capó-Vélez, Bryan Morales-Vargas, Aurian García-González, José G Grajales-Reyes, Manuel Delgado-Vélez, Bismark Madera, Carlos A Báez-Pagán, Orestes Quesada, José A Lasalde-Dominicci
Currently, there are no specific therapies to treat HIV-1 associated neurocognitive disorders (HAND). The HIV-1 envelope, gp120, induces neuropathological changes similar to those in HAND patients; furthermore, it triggers an upregulation of the α7-nicotinic acetylcholine receptor (α7-nAChR), facilitating intracellular calcium overload and neuronal cell death. Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that α7-nAChRs are upregulated on striatal neurons. Activation of α7-nAChRs leads to an increase in both intracellular calcium and percentage of apoptotic cells, which can be abrogated by antagonizing the receptor, suggesting a role for α7-nAChRs in gp120-induced neurotoxicity...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29376856/in-vivo-depiction-of-%C3%AE-7-nicotinic-receptor-loss-for-cognitive-decline-in-alzheimer-s-disease
#15
Kyoko Nakaizumi, Yasuomi Ouchi, Tatsuhiro Terada, Etsuji Yoshikawa, Akihiro Kakimoto, Takashi Isobe, Tomoyasu Bunai, Masamichi Yokokura, Katsuaki Suzuki, Yasuhiro Magata
BACKGROUND: The α7 subtype of the nicotinic acetylcholine receptor (nAChR) is considered important in higher cognitive functions, and cholinergic loss underpins the pathophysiology of Alzheimer's disease (AD). However, the relationships between α7 nAChR function and clinical functions or amyloid-β (Aβ) deposition remain to be explored in the living AD brain. OBJECTIVE: We aimed to elucidate the relationship between α7 nAChR availability in the specific cholinergic region and cognitive decline in the Aβ-confirmed AD brain...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29370396/ketamine-induced-prefrontal-serotonin-release-is-mediated-by-cholinergic-neurons-in-the-pedunculopontine-tegmental-nucleus
#16
Haruko Kinoshita, Naoya Nishitani, Yuma Nagai, Chihiro Andoh, Nozomi Asaoka, Hiroyuki Kawai, Norihiro Shibui, Kazuki Nagayasu, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko
Background: Ketamine rapidly elicits antidepressive effects in humans and mice, in which serotonergic activity is involved. Although α4β2 nicotinic acetylcholine receptor (α4β2 nAChR) in the dorsal raphe nucleus (DRN) plays a key role in the ketamine-induced prefrontal serotonin release, the source of cholinergic afferents and its role are unclear. Methods: Prefrontal serotonin levels after ketamine injection were measured by microdialysis in rats. Electrolytic lesion of pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) was made with constant direct current...
January 23, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29369741/reflex-bronchoconstriction-evoked-by-inhaled-nicotine-aerosol-in-guinea-pigs-role-of-the-nicotinic-acetylcholine-receptor
#17
Lu-Yuan Lee, Ruei-Lung Lin, Mehdi Khosravi, Fadi Xu
Inhaled cigarette smoke stimulated vagal bronchopulmonary C-fibers via an action of nicotine on neuronal nicotinic acetylcholine receptor (nAChR). Recent studies have reported that nicotine at high concentrations can also activate the transient receptor potential ankyrin 1 receptor (TRPA1) expressed in these sensory nerves. This study was carried out to characterize the airway response to inhaled nicotine aerosol and to investigate the relative roles of nAChR and TRPA1 in this response. Guinea pigs were anesthetized and mechanically ventilated; one tidal volume of nicotine aerosol (2% solution) was diluted by equal volume of air and delivered directly into the lung via a tracheal cannula in a single breath...
January 25, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29366967/monepantel-is-a-non-competitive-antagonist-of-nicotinic-acetylcholine-receptors-from-ascaris-suum-and-oesophagostomum-dentatum
#18
Melanie Abongwa, Djordje S Marjanovic, James G Tipton, Fudan Zheng, Richard J Martin, Sasa M Trailovic, Alan P Robertson
Zolvix® is a recently introduced anthelmintic drench containing monepantel as the active ingredient. Monepantel is a positive allosteric modulator of DEG-3/DES-2 type nicotinic acetylcholine receptors (nAChRs) in several nematode species. The drug has been reported to produce hypercontraction of Caenorhabditis elegans and Haemonchus contortus somatic muscle. We investigated the effects of monepantel on nAChRs from Ascaris suum and Oesophagostomum dentatum heterologously expressed in Xenopus laevis oocytes...
December 16, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29363414/molecular-interactions-of-type-i-and-type-ii-positive-allosteric-modulators-with-the-human-%C3%AE-7-nicotinic-acetylcholine-receptor-an-in-silico-study
#19
Katarzyna M Targowska-Duda, Agnieszka A Kaczor, Krzysztof Jozwiak, Hugo R Arias
The binding site locations and structural components for type I and type II positive allosteric modulators (PAMs) of the α7 nicotinic acetylcholine receptor (nAChR) have not been fully characterized yet. In this regard, homology models of the human α7 nAChR and hα7/m5-HT3A chimera, built using the crystal structure of the serotonin type 3A receptor (5-ΗΤ3ΑR), were used for molecular docking and molecular dynamics simulations to study the molecular interactions of selected type I (5-hydroxyindol, NS-1738, and LY-2087101) and type II (PNU-120596, PAM-2, and TBS-516) PAMs...
January 24, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29358666/inhibitory-circuit-gating-of-auditory-critical-period-plasticity
#20
Anne E Takesian, Luke J Bogart, Jeff W Lichtman, Takao K Hensch
Cortical sensory maps are remodeled during early life to adapt to the surrounding environment. Both sensory and contextual signals are important for induction of this plasticity, but how these signals converge to sculpt developing thalamocortical circuits remains largely unknown. Here we show that layer 1 (L1) of primary auditory cortex (A1) is a key hub where neuromodulatory and topographically organized thalamic inputs meet to tune the cortical layers below. Inhibitory interneurons in L1 send narrowly descending projections to differentially modulate thalamic drive to pyramidal and parvalbumin-expressing (PV) cells in L4, creating brief windows of intracolumnar activation...
January 22, 2018: Nature Neuroscience
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