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https://www.readbyqxmd.com/read/28445721/nacho-mediates-nicotinic-acetylcholine-receptor-function-throughout-the-brain
#1
Jose A Matta, Shenyan Gu, Weston B Davini, Brian Lord, Edward R Siuda, Anthony W Harrington, David S Bredt
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and β subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28444988/inhibitory-action-of-oxytocin-on-spontaneous-contraction-of-rat-distal-colon-by-nitrergic-mechanism-involvement-of-cyclic-gmp-and-apamin-sensitive-k-channels
#2
R Wang, M T Han, X L Lv, Y A Yu, S Q Chai, C M Qu, C Y Liu
AIM: The mechanisms underlying the inhibitory effects of oxytocin (OT) on colon tone are not totally understood. We explore the mechanisms of OT on spontaneous contractility in rat distal colon, and identify the mediators involved in this action. METHODS: In rat distal colon strips, mechanical activity was analyzed and the production of nitric oxide (NO) in tissue loaded with the fluorochrome DAF-FM was visualized by confocal microscopy. OT receptor (OTR) expression was determined by western blotting and immunofluorescence...
April 26, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#3
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440734/cholinergic-activation-suppresses-palmitate-induced-macrophage-activation-and-improves-acylation-stimulating-protein-resistance-in-co-cultured-adipocytes
#4
Jing Wu, Zhou-Yang Jiao, Rui-Zhen Li, Hui-Ling Lu, Hao-Hao Zhang, Katherine Cianflone
Acylation-stimulating protein (ASP), produced through activation of the alternative complement immune system, modulates lipid metabolism. Using a trans-well co-culture cell model, the mitigating role of α7-nicotinic acetylcholine receptor (α7nAChR)-mediated cholinergic pathway on ASP resistance was evaluated. ASP signaling in adipocytes via its receptor C5L2 and signaling intermediates Gαq, Gβ, phosphorylated protein kinase C-α, and protein kinase C-ζ were markedly suppressed in the presence of TNFα or medium from palmitate-treated RAW264...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28440223/structural-insights-into-the-molecular-mechanisms-of-myasthenia-gravis-and-their-therapeutic-implications
#5
Kaori Noridomi, Go Watanabe, Melissa N Hansen, Gye Won Han, Lin Chen
The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28438647/effects-of-bms-902483-an-%C3%AE-7-nicotinic-acetylcholine-receptor-partial-agonist-on-cognition-and-sensory-gating-in-relation-to-receptor-occupancy-in-rodents
#6
Rick L Pieschl, Regina Miller, Kelli M Jones, Debra J Post-Munson, Ping Chen, Kimberly Newberry, Yulia Benitex, Thaddeus Molski, Daniel Morgan, Ivar M McDonald, John E Macor, Richard E Olson, Yukiko Asaka, Siva Digavalli, Amy Easton, James Herrington, Ryan S Westphal, Nicholas J Lodge, Robert Zaczek, Linda J Bristow, Yu-Wen Li
The α7 nicotinic acetylcholine receptor is thought to play an important role in human cognition. Here we describe the in vivo effects of BMS-902483, a selective potent α7 nicotinic acetylcholine receptor partial agonist, in relationship to α7 nicotinic acetylcholine receptor occupancy. BMS-902483 has low nanomolar affinity for rat and human α7 nicotinic acetylcholine receptors and elicits currents in cells expressing human or rat α7 nicotinic acetylcholine receptors that are about 60% of the maximal acetylcholine response...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438486/pti-125-binds-and-reverses-an-altered-conformation-of-filamin-a-to-reduce-alzheimer-s-disease-pathogenesis
#7
Hoau-Yan Wang, Kuo-Chieh Lee, Zhe Pei, Amber Khan, Kalindi Bakshi, Lindsay H Burns
We show that amyloid-β1-42 (Aβ42) triggers a conformational change in the scaffolding protein filamin A (FLNA) to induce FLNA associations with α7-nicotinic acetylcholine receptor (α7nAChR) and toll-like receptor 4 (TLR4). These aberrant associations respectively enable Aβ42's toxic signaling via α7nAChR to hyperphosphorylate tau protein, and TLR4 activation to release inflammatory cytokines. PTI-125 is a small molecule that preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its α7nAChR/TLR4 associations and downstream pathologies...
March 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28436626/-the-role-of-central-cholinergic-system-in-epilepsy
#8
Ying Wang, Yi Wang, Zhong Chen
Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28436303/choline-supplementation-during-pregnancy-protects-against-gestational-lipopolysaccharide-induced-inflammatory-responses
#9
Min Zhang, Xinjia Han, Juejie Bao, Jinying Yang, Shao-Qing Shi, Robert E Garfield, Huishu Liu
OBJECTIVES: To estimate the effects and mechanisms of choline, an essential nutrient and a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, on the prevention of symptoms and the effects on the cholinergic anti-inflammatory pathways (CAP) in a lipopolysaccharide (LPS)-induced inflammatory response in a rat model. METHODS: Inflammation was induced by LPS treatment (1.0 μg LPS/kg body weight) on gestational day (GD) 14. Nonpregnant and pregnant Sprague Dawley rats were placed on a normal choline diet (1...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28433565/inhibitory-effects-of-pine-nodule-extract-and-its-component-sj-2-on-acetylcholine-induced-catecholamine-secretion-and-synthesis-in-bovine-adrenal-medullary-cells
#10
Xiaojia Li, Takafumi Horishita, Yumiko Toyohira, Hui Shao, Jie Bai, Haixia Bo, Xinbo Song, Shin Ishikane, Yukari Yoshinaga, Noriaki Satoh, Masato Tsutsui, Nobuyuki Yanagihara
Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0...
April 7, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28428759/morphological-regeneration-and-functional-recovery-of-neuromuscular-junctions-after-tourniquet-induced-injuries-in-mouse-hindlimb
#11
Huiyin Tu, Dongze Zhang, Ryan M Corrick, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Tourniquet application and its subsequent release cause serious injuries to the skeletal muscle, nerve, and neuromuscular junction (NMJ) due to mechanical compression and ischemia-reperfusion (IR). Monitoring structural and functional repair of the NMJ, nerve, and skeletal muscle after tourniquet-induced injuries is beneficial in exploring potential cellular and molecular mechanisms responsible for tourniquet-induced injuries, and for establishing effective therapeutic interventions. Here, we observed long-term morphological and functional changes of the NMJ in a murine model of tourniquet-induced hindlimb injuries...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28425312/activation-of-spinal-alpha-7-nicotinic-acetylcholine-receptor-shortens-the-duration-of-remifentanil-induced-postoperative-hyperalgesia-by-upregulating-kcc2-in-the-spinal-dorsal-horn-in-rats
#12
Wei Gu, Wei Zhang, Yishan Lei, Yin Cui, Shuaishuai Chu, Xiaoping Gu, Zhengliang Ma
Background Accumulating evidence has shown that the signal from spinal brain-derived neurotrophic factor/tyrosine receptor kinase B-K(+)-Cl(-) cotransporter-2 plays a critical role in the process of pain hypersensitivity. The activation of alpha-7 nicotinic acetylcholine receptors could have an analgesic effect on remifentanil-induced postoperative hyperalgesia. Nevertheless, whether intrathecal administration of PNU-120596, an alpha-7 nicotinic acetylcholine receptors selective type II positive allosteric modulator, before surgery could affect the duration of remifentanil-induced postoperative hyperalgesia remains unknown, and the effects of alpha-7 nicotinic acetylcholine receptors activation on the brain-derived neurotrophic factor/tyrosine receptor kinase B-K(+)-Cl(-) cotransporter-2 signal in the spinal dorsal horn of rats with remifentanil-induced postoperative hyperalgesia is still enigmatic...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28422078/antivenom-for-neuromuscular-paralysis-resulting-from-snake-envenoming
#13
REVIEW
Anjana Silva, Wayne C Hodgson, Geoffrey K Isbister
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information...
April 19, 2017: Toxins
https://www.readbyqxmd.com/read/28421441/n-methyl-serotonin-analogues-from-the-bufo-bufo-toad-venom-interact-efficiently-with-the-%C3%AE-7-nicotinic-acetylcholine-receptors
#14
E V Kryukova, D S Lebedev, I A Ivanov, D A Ivanov, V G Starkov, V I Tsetlin, Yu N Utkin
Two low-molecular-weight compounds were isolated from the parotid gland secret of the toad Bufo bufo, which by absorption spectra and HPLC-MS/MS chromatography data correspond to di- and trimethyl derivatives of serotonin (5-hydorxytryptamine): bufotenine (confirmed by counter synthesis) and bufotenidine (5-HTQ). In experiments on competitive radioligand binding, these compounds showed a higher affinity and selectivity for neuronal α7 nicotinic acetylcholine receptors compared with the muscular cholinergic receptors...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420996/chronic-water-pipe-smoke-exposure-induces-injurious-effects-to-reproductive-system-in-male-mice
#15
Badreldin H Ali, Khalid A Al Balushi, Mohammed Ashique, Asem Shalaby, Mohammed A Al Kindi, Sirin A Adham, Turan Karaca, Sumaya Beegam, Priya Yuvaraju, Abderrahim Nemmar
There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine-protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28420461/-%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-attenuated-the-lipopolysaccharide-induced-inflammatory-response-via-inhibiting-the-activation-of-nuclear-factor-%C3%AE-b
#16
Xingxing Shi, Jianhua Yao, Cheng Wang, Xijing Zhang
OBJECTIVE: To investigate the effects of α7 nicotinic acetylcholine receptor (α7nAChR) on the inflammatory response induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and its molecular mechanisms. METHODS: RAW264.7 macrophages were cultured in vitro. Inflammatory cell model was constructed by LPS stimulation. Cells were challenged by LPS (1, 10, 100 and 500 μg/L) for 5 hours or 100 μg/L LPS for 0, 2, 4, 8, 12, 24, 48 and 72 hours, and the release of tumor necrosis factor-α (TNF-α) was detected by the enzyme linked immunosorbent assay (ELISA)...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28420041/-18-f-nifene-test-retest-reproducibility-in-first-in-human-imaging-of-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors
#17
Patrick J Lao, Tobey J Betthauser, Dana L Tudorascu, Todd E Barnhart, Ansel T Hillmer, Charles K Stone, Jogeshwar Mukherjee, Bradley T Christian
The aim of this study was to examine the suitability of [(18) F]nifene, a novel α4β2* nicotinic acetylcholine receptor (nAChR) radiotracer, for in vivo brain imaging in a first-in-human study. METHODS: Eight healthy subjects (4M,4F;21-69,44±21yrs) underwent a [(18) F]nifene PET scan (200±3.7MBq), and seven underwent a second scan within 58±31days. Regional estimates of DVR were measured using the multilinear reference tissue model (MRTM2) with the corpus callosum as reference region...
April 18, 2017: Synapse
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#18
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419642/nicotine-induced-molecular-alterations-are-modulated-by-gabab-receptor-activity
#19
Andres P Varani, Valeria T Pedrón, Amira J Aon, Christian Höcht, Gabriela B Acosta, Bernhard Bettler, Graciela N Balerio
It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward effect; nevertheless, the mechanism implicated is not well known. In this regard, we evaluated the involvement of GABAB receptors on the behavioral, neurochemical, biochemical and molecular alterations associated with the rewarding effects induced by NIC in mice, from a pharmacological and genetic approach. NIC-induced rewarding properties (0.5 mg/kg, subcutaneously, sc) were evaluated by conditioned place preference (CPP) paradigm...
April 17, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28416445/%C3%AE-o-conotoxin-gexiva-disulfide-bond-isomers-exhibit-differential-sensitivity-for-various-nicotinic-acetylcholine-receptors-but-retain-potency-and-selectivity-for-the-human-%C3%AE-9%C3%AE-10-subtype
#20
Dongting Zhangsun, Xiaopeng Zhu, Quentin Kaas, Yong Wu, David J Craik, J Michael McIntosh, Sulan Luo
Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible isomers...
April 14, 2017: Neuropharmacology
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