Search results for "Nicotinic acetylcholine receptor"
showing 10 items of 50 documents
Closed-Locked and Apo-Resting State Structures of the Human α7 Nicotinic Receptor: A Computational Study
2018
International audience; Nicotinic acetylcholine receptors, belonging to the Cys-loop super-family of ligand-gated ion channels (LGICs), are membrane proteins present in neurons and at neuromuscular junctions. They are responsible for signal transmission, and their function is regulated by neurotransmitters, agonists and antagonists drugs. A detailed knowledge of their conformational transition in response to ligand binding is critical to understand the basis of ligand-receptor interaction, in view of new pharmacological approaches to control receptor activity. However, the scarcity of experimentally derived structures of human channels makes this perspective extremely challenging. To contri…
A possible desensitized state conformation of the human α7 nicotinic receptor: A molecular dynamics study
2017
International audience; The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing. The characterization of the desensitized conformation(s) is even more complex, and only few specific characteristics have been identified. Furthermore, exp…
Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures
2007
Nicotinic acetylcholine receptors play important roles in numerous cognitive processes as well as in several debilitating central nervous system (CNS) disorders. In order to fully elucidate the diverse roles of nicotinic acetylcholine receptors in CNS function and dysfunction, a detailed knowledge of their cellular and subcellular localizations is essential. To date, methods to precisely localize nicotinic acetylcholine receptors in the CNS have predominantly relied on the use of anti-receptor subunit antibodies. Although data obtained by immunohistology and immunoblotting are generally in accordance with ligand binding studies, some discrepancies remain, in particular with electrophysiolog…
Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans.
2009
Polymorphisms in the CHRNA4 gene coding the nicotinic acetylcholine receptor subunit alpha 4 have recently been suggested to play a role in the determination of smoking-related phenotypes. To examine this hypothesis, we conducted a genetic association study in three large samples from the German general population (N(1)=1412; N(2)=1855; N(3)=2294). Five single-nucleotide polymorphisms in CHRNA4 were genotyped in 5561 participants, including 2707 heavily smoking cases (regularly smoking at least 20 cigarettes per day) and 2399 never-smoking controls (or=100 cigarettes over lifetime). We examined associations of the polymorphisms with smoking case-control status and with the extent of nicotin…
Cellular distribution of nicotinic acetylcholine receptor subunit mRNAs in the human cerebral cortex as revealed by non-isotopic in situ hybridizatio…
1994
The pharmacology of telencephalic nicotinic acetylcholine receptors (nAChRs) has become an important issue in recent years. While in the human brain a direct pharmacological assessment is difficult to achieve the visualization of nAChRs has been enabled by histochemical techniques providing an ever increasing and improving resolution. Receptor autoradiography was used to visualize binding sites on the level of cortical layers whereas immunohistochemistry has allowed for the cell type-specific and ultrastructural localization of receptor protein. Further investigations have to elucidate the cellular sites of NAChR biosynthesis by visualizing subunit-specific transcripts. Using autopsy sample…
Increased sensitivity of the neuronal nicotinic receptor alpha-2 subunit causes familial epilepsy with nocturnal wandering and ictal fear
2006
Sleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the α4 and β2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep …
Smoking cessation and variations in nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 genes.
2009
Background Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits α-5, α-3, and β-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation. Methods Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who…
Behavioral effects of different enriched environments in mice treated with the cholinergic agonist PNU-282987.
2013
Abstract Environmental enrichment is an experimental model in which rodents are housed in complex environments that favor lower levels of anxiety-like behavior. PNU-282987 (PNU) is a α7 nicotinic acetylcholine receptor agonist with beneficial effects on learning though its effects on anxiety are unclear. Our main aim was to carry out a study of its effects in NMRI ( n = 96) mice reared in different environments: environmental enrichment (EE), Marlau™ cages (MC) and standard environment (SE). After a 4-month period, mice received acute treatment of PNU (2.5, 5 and 10 mg/kg) and were evaluated in the elevated plus-maze (EPM) and hole-board (HB). In the EPM, both EE and MC reared mice showed …
Introductory Lecture: Allosteric Modulation of Torpedo Nicotinic Acetylcholine Receptor Ion Channel Activity by Noncompetitive Agonists
1997
AbstractSimilar to other neuroreceptors of the vertebrate central nervous system, the nicotinic acetylcholine receptor (nAChR) is subject to modulatory control by allosterically acting ligands. Of particular interest in this regard are allosteric ligands that enhance the sensitivity of the receptor to its natural agonist acetylcholine (ACh), as such ligands could be useful as drugs in diseases associated with impaired nicotinic neurotransmission. Here we discuss the action of a novel class of nAChR ligands which act as allosterically potentiating ligands (APL) on the nicotinic responses induced by ACh and competitive agonists. In addition, APLs also act as noncompetitive agonists of very lo…
The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions
2000
The present experiments were designed to extend previous work showing that acute intermittent (-)nicotine treatment upregulates the level of fibroblast growth factor-2 (FGF2) mRNA in several rat brain regions, by the use of the nicotinic acetylcholine receptor (nAChR) agonist ABT-594 with preferential selectivity for the alpha4beta2 nAChR subtype. ABT594 treatment led to a well-defined temporal and regional upregulation of FGF-2 mRNA. A double labelling analysis showed that the up-regulation of FGF-2 mRNA involves both neuronal and non-neuronal cells. The effects of ABT-594 on FGF-2 expression were antagonized by the preferential alpha4beta2 antagonist dihydrobetaerythroidine (DHbetaE), but…