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Hannah Hesselbach, Ricarda Scheiner
Due to intensive agriculture honeybees are threatened by various pesticides. The use of one group of them, the neonicotinoids, was recently restricted by the European Union. These chemicals bind to the nicotinic acetylcholine receptor (nAchR) in the honeybee brain. Recently, Bayer AG released a new pesticide by the name of "Sivanto" against sucking insects. It is assumed to be harmless for honeybees, although its active ingredient, flupyradifurone, binds nAchR similar to the neonicotinoids. We investigated if this pesticide affects the taste for sugar and cognitive performance in honeybee foragers...
March 21, 2018: Scientific Reports
Asti Jackson, Roger L Papke, M Imad Damaj
RATIONALE: Recent preclinical data has implicated the α7 nicotinic acetylcholine receptor (nAChR) as a target in modulating nicotine reward. However, the role of the channel properties of the α7 nAChR in nicotine withdrawal is unknown. OBJECTIVES: This study aimed to investigate the impact of α7 nAChR pharmacological modulation on mecamylamine-precipitated nicotine withdrawal behaviors in mice by using positive allosteric modulators (PAMs). METHODS: The effect of the orthosteric α7 nAChR full agonist PNU282987 (1, 3, 9 mg/kg, s...
March 16, 2018: Psychopharmacology
Alan S Lewis, Gerrit Ian van Schalkwyk, Mayra Ortiz Lopez, Fred R Volkmar, Marina R Picciotto, Denis G Sukhodolsky
Nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR, are implicated in the pathophysiology of both autism spectrum disorder (ASD) and aggressive behavior. We explored the feasibility, tolerability, and preliminary efficacy of targeting nAChRs using transdermal nicotine to reduce aggressive symptoms in adults with ASD. Eight subjects were randomized in a double-blind crossover trial of 7 mg transdermal nicotine or placebo, each for 1 week. All participants tolerated nicotine treatment well...
March 13, 2018: Journal of Autism and Developmental Disorders
Lorena Colás, Maria Domercq, Pedro Ramos-Cabrer, Ana Palma, Vanessa Gómez-Vallejo, Daniel Padro, Sandra Plaza-García, Krishna R Pulagam, Makoto Higuchi, Carlos Matute, Jordi Llop, Abraham Martín
In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [11 C]NS14492 and immunohistochemistry (IHC)...
March 12, 2018: Glia
Waranyoo Phoolcharoen, Ashley C Banyard, Christophe Prehaud, David Selden, Guanghui Wu, Colin P D Birch, Tim H Szeto, Monique Lafon, Anthony R Fooks, Julian K-C Ma
Rabies causes more than 60,000 human deaths annually in areas where the virus is endemic. Importantly, rabies is one of the few pathogens for which there is no treatment following the onset of clinical disease with the outcome of infection being death in almost 100% of cases. Whilst vaccination, and the combination of vaccine and rabies immunoglobulin treatment for post-exposure administration are available, no tools have been identified that can reduce or prevent rabies virus replication once clinical disease has initiated...
March 6, 2018: Vaccine
Dean F Wong, Hiroto Kuwabara, Andrew G Horti, Joshua M Roberts, Ayon Nandi, Nicola Casella, James Brasic, Elise M Weerts, Kelly Kitzmiller, Jenny A Phan, Lorena Gapasin, Akira Sawa, Heather Valentine, Gary Wand, Noble George, Michael McDonald, William Kem, Robert Freedman, Albert Gjedde
Background: The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7-nAChR suggests a role in cognition. Methods: We expanded the first-in-human PET imaging of α7-nAChR with [18F]ASEM from five to 21 healthy non-smoking volunteers and added a feasibility study in six male patients with schizophrenia. Study aims included 1) confirmation of test-retest reproducibility of [18F]ASEM binding, 2) demonstration of specificity by competition with DMXB-A, an α7-nAChR partial agonist, 3) estimation of [18F]ASEM binding potentials and α7-nAChR density in vivo in humans, and 4) demonstrating the feasibility of studying α7-nAChR as a target for schizophrenia...
March 7, 2018: International Journal of Neuropsychopharmacology
Toshio Takahashi, Akira Shiraishi, Jun Murata
Cholinergic signaling, which modulates cell activities via nicotinic and muscarinic acetylcholine receptors (n- and mAChRs) in response to internal or external stimuli, has been demonstrated in mammalian non-neuronal cells that synthesize acetylcholine (ACh). One of the major pathways of excitatory transmission in the enteric nervous system (ENS) is mediated by cholinergic transmission, with the transmitter ACh producing excitatory potentials in postsynaptic effector cells. In addition to ACh-synthesizing and ACh-metabolizing elements in the ENS, the presence of non-neuronal ACh machinery has been reported in epithelial cells of the small and large intestines of rats and humans...
March 5, 2018: International Journal of Molecular Sciences
E N Lyukmanova, M L Bychkov, G V Sharonov, A V Efremenko, M A Shulepko, D S Kulbatskii, Z O Shenkarev, A V Feofanov, D A Dolgikh, M P Kirpichnikov
BACKGROUND AND PURPOSE: Nicotinic acetylcholine receptors (nAChRs) are a promising target for development of new anticancer therapies. Our purpose is to study effects of human proteins SLURP-1 and SLURP-2, antagonists of nAChRs, on human epithelial cancer cells. EXPERIMENTAL APPROACH: Growth of epithelial cancer cells (A431, SKBR3, MCF-7, A549, HT-29) exposed to SLURP-1, SLURP-2, mecamylamine, atropine, timolol and gefitinib was investigated by WST-1 test. Expression levels of SLURP-1, α7-nAChR and EGF receptors and their distribution in cancer cells were studied by confocal microscopy and flow cytometry...
March 5, 2018: British Journal of Pharmacology
Candace Jones
PURPOSE: The aim of this article is to review the recent trials of α7 nicotinic acetylcholine receptor (α7 nAChR) agonists and positive allosteric modulators (PAMs) on the treatment of cognitive decline in schizophrenia. α7 Nicotinic acetylcholine receptor abnormalities in schizophrenia and clinical implications of α7 nAChR agonists and PAMs are also discussed. PROCEDURES: Studies were searched on PubMed with keywords "nicotinic," "alpha7," and "schizophrenia" over a 2-year period: January 1, 2016, to December 1, 2017...
March 2, 2018: Journal of Clinical Psychopharmacology
Mohamed R Elnagar, Anne Byriel Walls, Gouda K Helal, Farid M Hamada, Morten Skøtt Thomsen, Anders A Jensen
In the present study, the functional properties of α7 nicotinic acetylcholine receptors (α7 nAChRs) and N-methyl-D-aspartate receptors (NMDARs) endogenously expressed in SH-SY5Y human neuroblastoma cells were characterized in an extracellular-signal regulated kinase (ERK) phosphorylation assay. Both choline and N-methyl-D-aspartate (NMDA) mediated robust concentration-dependent increases in ERK phosphorylation in the SH-SY5Y cells, exhibiting EC50 values in good agreement with those reported for the agonists at recombinant α7 nAChRs and NMDARs, respectively...
March 1, 2018: European Journal of Pharmacology
Shugo Suzuki, Samuel M Cohen, Lora L Arnold, Hiroyuki Kato, Satoshi Fuji, Karen L Pennington, Yuko Nagayasu, Aya Naiki-Ito, Yoriko Yamashita, Satoru Takahashi
Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. Cigarette smoke inhalation in mice and orally administered nicotine in rats and mice increased urothelial cell proliferation. Nicotine, a major component of smoke, induced cell proliferation in multiple cell types in vitro. In the present study, the enhancing effects of nicotine on F344 rat bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Nicotine administered in drinking water for 32 weeks following 4 weeks of BBN treatment significantly increased the incidence and number of urothelial carcinomas dose-dependently...
February 28, 2018: Toxicology
Jaimee A Domville, John E Baenziger
The mechanisms underlying lipid-sensing by membrane proteins is of considerable biological importance. A unifying mechanistic question is how a change in structure at the lipid-protein interface is translated through the transmembrane domain to influence structures critical to protein function. Gating of the nicotinic acetylcholine receptor (nAChR) is sensitive to its lipid environment. To understand how changes at the lipid-protein interface influence gating, we examined how a mutation at position 418 on the lipid-facing surface of the outer most M4 transmembrane α-helix alters the energetic couplings between M4 and the remainder of the transmembrane domain...
March 1, 2018: Scientific Reports
Jennifer Marie Coughlin, Stephanie Slania, Yong Du, Hailey B Rosenthal, Wojciech G Lesniak, Il Minn, Gwenn S Smith, Robert F Dannals, Hiroto Kuwabara, Dean F Wong, Yuchuan Wang, Andrew G Horti, Martin G Pomper
Reduced density of the α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) in the cortex and hippocampus of human brain has been reported in aging and patients with neurodegenerative disease. This study assessed the pharmacokinetic behavior of18 F-XTRA, a new radiotracer for in vivo positron emission tomography (PET) imaging of the α4β2-nAChR, particularly in extrathalamic regions of interest (ROIs) where the α4β2-nAChR is less densely expressed than in thalamus.18 F-XTRA was also used to evaluate the α4β2-nAChR in hippocampus in human aging...
March 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Muriel Amar, Rómulo Aráoz, Bogdan I Iorga, Takeshi Yasumoto, Denis Servent, Jordi Molgó
Prorocentrolides are members of the cyclic imine phycotoxins family. Their chemical structure includes a 26-membered carbo-macrocycle and a 28-membered macrocyclic lactone arranged around a hexahydroisoquinoline that incorporates the characteristic cyclic imine group. Six prorocentrolides are already known. However, their mode of action remains undetermined. The aim of the present work was to explore whether prorocentrolide A acts on nicotinic acetylcholine receptors (nAChRs), using competition-binding assays and electrophysiological techniques...
February 28, 2018: Toxins
Jin Zhou, Fulin Liu, Luting Yu, Dan Xu, Bin Li, Guohui Zhang, Wen Huang, Lu Li, Yuanzhen Zhang, Wei Zhang, Hui Wang
Impaired placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity which inactivates maternal glucocorticoids is associated with poor fetal growth and a higher risk of chronic diseases in adulthood. This study aimed to elucidate the epigenetically regulatory mechanism of nicotine on placental 11β-HSD2 expression. Pregnant Wistar rats were administered 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 9 to 20. The results showed that prenatal nicotine exposure increased corticosterone levels in the placenta and fetal serum, disrupted placental morphology and endocrine function, and reduced fetal bodyweight...
February 24, 2018: Toxicology and Applied Pharmacology
Hiroki Toyoda
The insular cortex is known to play a pivotal role in addiction to nicotine. Long-term depression (LTD) in the central nervous system is a major form of synaptic plasticity which is involved in learning and memory and in various pathological conditions such as nicotine addiction. Until now, effects of nicotine on LTD were mainly examined in the hippocampus and striatum, and there is no report showing the effects of nicotine on LTD in the insular cortex. In the present study, I show for the first time that nicotine facilitates LTD which is induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training) in layer 5 pyramidal neurons of the mouse insular cortex using whole-cell patch-clamp recordings...
February 22, 2018: Neuroscience Letters
Yann S Mineur, Emma L Cahuzac, Tenna N Mose, Matthew P Bentham, Margreet E Plantenga, David C Thompson, Marina R Picciotto
Medications that target the noradrenergic system are important therapeutics for depression and anxiety disorders. More recently, clinical studies have shown that the α2-noradrenergic receptor (α2AR) agonist guanfacine can decrease stress-induced smoking relapse during acute abstinence, suggesting that targeting the noradrenergic system may aid in smoking cessation through effects on stress pathways in the brain. Acetylcholine (ACh), like the nicotine in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) to regulate behaviors related to anxiety and depression...
February 22, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Friedrich-Alexander Ludwig, Steffen Fischer, René Smits, Winnie Deuther-Conrad, Alexander Hoepping, Solveig Tiepolt, Marianne Patt, Osama Sabri, Peter Brust
Both (+)-[18 F]flubatine and its enantiomer (-)-[18 F]flubatine are radioligands for the neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). In a clinical study in patients with early Alzheimer's disease, (+)-[18 F]flubatine ((+)-[18 F] 1 ) was examined regarding its metabolic fate, in particular by identification of degradation products detected in plasma and urine. The investigations included an in vivo study of (+)-flubatine ((+)- 1 ) in pigs and structural elucidation of formed metabolites by LC-MS/MS...
February 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sarah E Maggio, Meredith A Saunders, Thomas A Baxter, Kimberly Nixon, Mark A Prendergast, Guangrong Zheng, Peter Crooks, Linda P Dwoskin, Rachel D Slack, Amy H Newman, Richard L Bell, Michael T Bardo
RATIONALE: Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. OBJECTIVES: Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs...
February 18, 2018: Psychopharmacology
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
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