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Nicotinic Acetylcholine Receptor Function
Published by Anonymous on 2007/9/30 (3054 reads)
1: AAPS J. 2006 Jan 13;7(4):E885-94.


Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells.

Gahring LC, Rogers SW.

Geriatric Research Education and Clinical Center, Salt Lake City VAMC, Salt Lake City, Utah 84132, USA. Lorise.Gahring@hsc.utah.edu

Of the thousands of proven carcinogens and toxic agents contained within a cigarette, nicotine, while being the addictive agent, is often viewed as the least harmful of these compounds. Nicotine is a lipophilic molecule whose effects on neuronal nicotinic acetylcholine receptors (nAChR) have been primarily focused on its physiologic impact within the confines of the brain and peripheral nervous system. However, recently, many studies have found neuronal nAChRs to be expressed on many different nonneuronal cell types throughout the body, where increasing evidence suggests they have important roles in determining the consequences of nicotine use on multiple organs systems and diseases as diverse as ulcerative colitis, chronic pulmonary obstructive disease, and diabetes, as well as the neurologic disorders of Parkinson's and Alzheimer's disease. This review highlights current evidence for the expression of peripheral nAChRs in cells other than neurons and how they participate in fundamental processes, such as inflammation. Understanding these processes may offer novel therapeutic strategies to approach inflammatory diseases, as well as precautions in the design of interventional drugs.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

PMID: 16594641 [PubMed - indexed for MEDLINE]

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2: Anat Rec A Discov Mol Cell Evol Biol. 2006 Apr;288(4):424-34.


Nicotinic acetylcholine receptor structure and function in the efferent auditory system.

Lustig LR.

Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, California 941430, USA. llustig@ohns.ucsf.edu

This article reviews and presents new data regarding the nicotinic acetylcholine receptor subunits alpha9 and alpha10. Although phylogentically ancient, these subunits have only recently been identified as critical components of the efferent auditory system and medial olivocochlear pathway. This pathway is important in auditory processing by modulating outer hair cell function to broadly tune the cochlea and improve signal detection in noise. Pharmacologic properties of the functionally expressed alpha9alpha10 receptor closely resemble the cholinergic response of outer hair cells. Molecular, immunohistochemical, and knockout mice studies have added further weight to the role this receptor plays in mediating the efferent auditory response. Alternate and complementary mechanisms of outer hair cell efferent activity might also be mediated through the nAChR alpha9alpha10, either through secondary calcium stores, second messengers, or direct protein-protein interactions. We investigated protein-protein interactions using a yeast-two-hybrid screen of the nAChR alpha10 intracellular loop against a rat cochlear cDNA library. Among the identified proteins was prosaposin, a precursor of saposins, which have been shown to act as neurotrophic factors in culture, can bind to a putative G0-coupled cell surface receptor, and may be involved in the prevention of cell death. This study and review suggest that nAChR alpha9alpha10 may represent a potential therapeutic target for a variety of ear disorders, including preventing or treating noise-induced hearing loss, or such debilitating disorders as vertigo or tinnitus. Copyright 2006 Wiley-Liss, Inc.

Publication Types:
Review

PMID: 16550589 [PubMed - indexed for MEDLINE]

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3: Brain Res Brain Res Rev. 2004 Dec;47(1-3):71-95.


Structural basis for lipid modulation of nicotinic acetylcholine receptor function.

Barrantes FJ.

UNESCO Chair of Biophysics and Molecular Neurobiology. rtfjb1@criba.edu.ar

The nicotinic acetylcholine receptor (AChR) is the archetype molecule in the superfamily of ligand-gated ion channels (LGIC). Members of this superfamily mediate fast intercellular communication in response to endogenous neurotransmitters. This review is focused on the structural and functional crosstalk between the AChR and lipids in the membrane microenvironment, and the modulation exerted by the latter on ligand binding and ion translocation. Experimental approaches using Laurdan extrinsic fluorescence and Förster-type resonance energy transfer (FRET) that led to the characterization of the polarity and molecular dynamics of the liquid-ordered phase AChR-vicinal lipids and the bulk membrane lipids, and the asymmetry of the AChR-rich membrane are reviewed first. The topological relationship between protein and lipid moieties and the changes in physical properties induced by exogenous lipids are discussed next. This background information lays the basis for understanding the occurrence of lipid sites in the AChR transmembrane region, and the selectivity of the protein-lipid interactions. Changes in FRET efficiency induced by fatty acids, phospholipid and cholesterol (Chol), led to the identification of discrete sites for these lipids on the AChR protein, and electron-spin resonance (ESR) spectroscopy has recently facilitated determination of the stoichiometry and selectivity for the AChR of the shell lipid. The influence of lipids on AChR function is discussed next. Combined single-channel and site-directed mutagenesis data fostered the recognition of lipid-sensitive residues in the transmembrane region, dissecting their contribution to ligand binding and channel gating, opening and closing. Experimental evidence supports the notion that the interface between the protein moiety and the adjacent lipid shell is the locus of a variety of pharmacologically relevant processes, including the action of steroids and other lipids.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 15572164 [PubMed - indexed for MEDLINE]

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4: Eur J Biochem. 2004 Jun;271(12):2305-19.


Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes.

Nicke A, Wonnacott S, Lewis RJ.

Max Planck-Institute for Brain Research, Frankfurt, Germany. nicke@mpih-frankfurt.mpg.de

Cone snails comprise approximately 500 species of venomous molluscs, which have evolved the ability to generate multiple toxins with varied and often exquisite selectivity. One class, the alpha-conotoxins, is proving to be a powerful tool for the differentiation of nicotinic acetylcholine receptors (nAChRs). These comprise a large family of complex subtypes, whose significance in physiological functions and pathological conditions is increasingly becoming apparent. After a short introduction into the structure and diversity of nAChRs, this overview summarizes the identification and characterization of alpha-conotoxins with selectivity for neuronal nAChR subtypes and provides examples of their use in defining the compositions and function of neuronal nAChR subtypes in native vertebrate tissues.

Publication Types:
Review

PMID: 15182346 [PubMed - indexed for MEDLINE]

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5: Tanpakushitsu Kakusan Koso. 2004 Jan;49(1):1-10.


[The structure and function of nicotinic acetylcholine receptor]

[Article in Japanese]

Miyazawa A, Fujiyoshi Y.

atsuo@spring8.or.jp

Publication Types:
Review

PMID: 14748133 [PubMed - indexed for MEDLINE]

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6: Prog Brain Res. 2004;145:109-20.


The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex.

Alkondon M, Albuquerque EX.

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA. malko001@umaryland.edu

Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central nervous system and have been implicated in multiple behavioral paradigms and pathological conditions. Nicotinic therapeutic interventions require an extensive characterization of native nAChRs including mapping of their distribution and function in different brain regions. Here, we describe the roles played by different nAChRs in affecting neuronal activity in the hippocampus and cerebral cortex. At least three distinct functional nAChR subtypes (alpha 7, alpha 4 beta 2, alpha 3 beta 4) can be detected in the hippocampal region, and in many instances a single neuron type is found to be influenced by all three nAChRs. Further, it became clear that GABAergic and glutamatergic inputs to the hippocampal interneurons are modulated via different subtypes of nAChRs. In the cerebral cortex, GABAergic inhibition to the layer V pyramidal neurons is enhanced predominantly via activation of alpha 4 beta 2 nAChR and to a minor extent via activation of alpha 7 nAChR. Such diversity offers pathways by which nicotinic drugs affect brain function.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 14650910 [PubMed - indexed for MEDLINE]

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7: Ann N Y Acad Sci. 2003 Sep;998:81-92.


Structure and function of AChBP, homologue of the ligand-binding domain of the nicotinic acetylcholine receptor.

Smit AB, Brejc K, Syed N, Sixma TK.

Department of Molecular and Cellular Neurobiology, Faculty of Biology, Research Institute Neurosciences Vrije Universiteit, Amsterdam, The Netherlands. absmit@bio.vu.nl

Acetylcholine-binding protein (AChBP) is a novel protein with high similarity to the extracellular domain of the nicotinic acetylcholine receptor. AChBP lacks the transmembrane domains and intracellular loops typical for the nAChRs. AChBP is secreted from glia cells in the central nervous system of the freshwater snail, Lymnaea stagnalis, where it modulates synaptic transmission. AChBP forms homopentamers with pharmacology that resembles the alpha(7)-type of nicotinic receptors. As such, AChBP is a good model for the ligand-binding domain of the nAChRs. In the crystal structure of AChBP at 2.7 A, each protomer has a modified immunoglobulin fold. Almost all residues previously shown to be involved in ligand binding in the nicotinic receptor are found in a pocket at the subunit interface, which is lined with aromatic residues. The AChBP crystal structure explains many of the biochemical studies on the nicotinic acetylcholine receptors. Surprisingly, the interface between protomers is relatively weakly conserved between families in the superfamily of pentameric ligand-gated ion channels. The lack of conservation has implications for the mechanism of gating of the ion channels.

Publication Types:
In Vitro
Review

PMID: 14592865 [PubMed - indexed for MEDLINE]

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8: Curr Opin Drug Discov Devel. 2003 Sep;6(5):620-32.


Modulation of nicotinic acetylcholine receptor function through the outer and middle rings of transmembrane domains.

Barrantes FJ.

Instituto de Investigaciones Bioquímicas, Universidad Nacional del Sur-CONICET CC 857, F8000FWB Bahía Blanca, Argentina. rtfjb1@criba.edu.ar

The photoaffinity labeling of amino acid residues embedded in the lipid bilayer, in combination with site-directed mutagenesis and patch-clamp electrophysiology, are beginning to delineate a topographic map of lipid-sensitive residues in the transmembrane (TM) region of the nicotinic acetylcholine receptor (nAChR), and to dissect their contribution to channel gating, opening and closing mechanisms. Recent structural data reveal that the TM segments form three concentric layers around the ion channel. An inner ring, shaped by five M2 segments (one from each subunit) excluded from contact with the lipid, forms the walls of the channel. The middle ring is formed by M1 and M3 segments, which exhibit contact with lipids, and the M4 membrane-embedded domains constitute an outer ring, distant from the channel and loosely separated from the middle ring. Although they are not part of the ion conduction pathway, the lipid-exposed middle and outer rings significantly modulate nAChR function. Sterols and steroids, in particular, are among the ligands that act on this functionally relevant moiety of the nAChR. A major challenge for the future is to elucidate the mechanism of propagation of information from the lipid-exposed TM rings to the rest of the receptor molecule.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 14579511 [PubMed - indexed for MEDLINE]

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9: Br J Pharmacol. 2003 Jul;139(6):1061-73.


Modulation of neuronal nicotinic receptor function by the neuropeptides CGRP and substance P on autonomic nerve cells.

Di Angelantonio S, Giniatullin R, Costa V, Sokolova E, Nistri A.

Biophysics Sector and INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 4, 34014 Trieste, Italy.

1. One classical example of how neuropeptides can affect the function of ligand-gated receptors is the modulation of neuronal nicotinic receptors (nAChRs) by substance P. The present review updates current understanding of this action by substance P and compares it with other neuropeptides more recently found to modulate nAChRs in the autonomic nervous system. 2. Calcitonin gene-related peptide (CGRP) and its N-terminal fragments have been shown to exert complex inhibitory as well facilitatory actions on nAChRs. Fragments such as CGRP(1-4), CGRP(1-5) and CGRP(1-6) rapidly and reversibly enhance agonist sensitivity of nAChRs without directly activating those receptors. Longer fragments or the full-length peptide potently inhibit responses mediated by nAChRs via an apparently competitive-type antagonism. This phenomenon differs from the substance P-induced block, which is agonist use-dependent and preferential towards large nicotinic responses. 3. It is argued that the full-length peptides CGRP and substance P might play distinct roles in the activity-dependent modulation of cholinergic neurotransmission, by inhibiting background noise in the case of CGRP or by reducing excessive excitation in the case of substance P. Hence, multiple neuropeptide mechanisms may represent a wide array of fine-tuning processes to regulate nicotinic synaptic transmission. 4. The availability of novel CGRP derivatives with a strong enhancing action on nAChRs may offer new leads for the drug design targeted for potentiation of nAChRs in the autonomic nervous system as well as in the brain, a subject of interest to counteract the deficit of the nAChR function associated with neurodegenerative diseases like Alzheimer's and Parkinson's diseases.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12871824 [PubMed - indexed for MEDLINE]

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10: Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):359-85.


Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure.

Gentry CL, Lukas RJ.

Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona 85013, USA.

Recent advances concerning effects of chronic nicotine exposure on nicotinic acetylcholine receptor (nAChR) expression are reviewed. Implications are assessed of these findings for roles of nAChR in health and disease and for design of drugs for treatment of neurological and psychiatric disorders. Most studies continue to show that chronic nicotine exposure induces increases in numbers of nAChR-like binding or antigenic sites ("upregulation") across all nAChR subtypes investigated, but with time- and dose-dependencies and magnitudes for these effects that are unique to subsets of nAChR subtypes. These effects appear to be post-transcriptionally based, but mechanisms involved remain obscure. With notable exceptions, most studies also show that chronic nicotine exposure induces several phases of nAChR functional loss ("desensitization" and longer-lasting "persistent inactivation") assessed in response to acute nicotinic agonist challenges. Times for onset and recovery and dose-dependencies for nicotine-induced functional loss also are nAChR subtype-specific. Some findings suggest that upregulation and functional loss are not causally- or mechanistically-related. It is suggested that upregulation is not as physiologically significant in vivo as functional effects of chronic nicotine exposure. By contrast, brain levels of nicotine in tobacco users, and perhaps levels of acetylcholine in the extracellular space, clearly are in the range that would alter the balance between nAChR in functionally ready or inactivated states. Further work is warranted to illuminate how effects of chronic nicotinic ligand exposure are integrated across nAChR subtypes and the neuronal circuits and chemical signaling pathways that they service to produce nicotine dependence and/or therapeutic benefit.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12769610 [PubMed - indexed for MEDLINE]

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11: Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):331-6.


Nicotinic receptor mutant mice in the study of autonomic function.

De Biasi M.

Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3498, USA. debiasi@bcm.tmc.edu

Nicotinic acetylcholine receptors (nAChRs) have been implicated in Alzheimer's disease, Parkinson's disease, epilepsy, nicotine addiction, schizophrenia, and autonomic dysfunctions. Although nicotine may be used therapeutically either alone or in association with other drugs, its beneficial effects are limited by its addictive properties and a number of other side effects. A deeper understanding of nicotinic cholinergic mechanisms is necessary to develop nAChR ligands that are more selective, less toxic, and more therapeutically effective than nicotine. Although there has been significant progress identifying the nAChR subunits that form functional nAChRs, there is limited information associating the location and function of nAChR subtypes in the nervous system. Several groups have genetically engineered mice in which one or more genes encoding nAChR subunits has been deleted or altered. Mice with nAChR mutations targeted to subunits that are highly expressed in the CNS have brought insight into the nAChR mechanisms involved in nicotine addiction, analgesia, aging, and nicotine-induced behaviors. Mutations targeted to nAChR subunits that are highly expressed in the peripheral nervous system have opened a window on the complex mechanisms governing autonomic control of peripheral organs. This review examines nAChRs in the autonomic control of peripheral organ systems as gleaned from studies of nAChR mutant mice.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12769607 [PubMed - indexed for MEDLINE]

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12: J Neurobiol. 2002 Dec;53(4):633-40.


Nicotinic receptor subtypes and cognitive function.

Levin ED.

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Neurobehavioral Research Laboratory, Box 3412, Durham, North Carolina 27710, USA. edlevin@duke.edu

Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine-induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either alpha 4 beta 2 or alpha 7 antagonists. Ventral hippocampal alpha 4 beta 2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal alpha 7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, alpha 4 beta 2 and alpha 7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, alpha 7 antagonist cotreatment actually reversed the working memory impairment caused by alpha 4 beta 2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction. Copyright 2002 Wiley Periodicals, Inc.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12436426 [PubMed - indexed for MEDLINE]

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13: Trends Pharmacol Sci. 2000 Jun;21(6):211-7.


Nicotinic receptor function: new perspectives from knockout mice.

Cordero-Erausquin M, Marubio LM, Klink R, Changeux JP.

CNRS UA D1284- 'Neurobiologie Moléculaire', Institut Pasteur, 28, rue du Dr Roux, 75724 Paris Cédex 15, France. cordero@pasteur.fr

Knockout mice, in which one or more genes of interest are silenced, provide unique opportunities to analyse diverse aspects of gene function in vivo. In particular, the contribution of the encoded protein(s) in complex behaviours can be assessed. Since the first targeted disruption in 1995 of the gene encoding the beta2-subunit of the nicotinic acetylcholine receptor (nAChR), all but a few of the mammalian nAChR subunits have been disrupted (i.e. alpha7, alpha4, alpha3, alpha9, beta4 and beta3). Recent advances brought by genetically modified mice to our understanding of the endogenous composition and role of nAChRs in the nervous system, and of the diverse pharmacological actions of nicotine regarding learning, analgesia, reinforcement, development and aging in the brain will be discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 10838608 [PubMed - indexed for MEDLINE]

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14: Schizophr Bull. 1996;22(3):431-45.


Nicotinic receptor function in schizophrenia.

Leonard S, Adams C, Breese CR, Adler LE, Bickford P, Byerley W, Coon H, Griffith JM, Miller C, Myles-Worsley M, Nagamoto HT, Rollins Y, Stevens KE, Waldo M, Freedman R.

Dept. of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.

Schizophrenia can be partially characterized by deficits in sensory processing. Biochemical, molecular, and genetic studies of one such endophenotype, the P50 auditory-evoked potential gating deficit, suggest that one of the neuronal nicotinic receptors, the alpha 7 nicotinic receptor, may function in an inhibitory neuronal pathway involved in this phenotype. The P50 deficit is normalized in nongating subjects by nicotine. Although most schizophrenia patients are heavy smokers, the effects of nicotine may be transient, as alpha 7 receptors are known to desensitize rapidly. In an animal model of the P50 gating deficit, antagonists of the alpha 7 nicotinic receptor block normal gating of the second of paired auditory stimuli. Regional localization of receptor expression includes areas known to function in sensory filtering. An inhibitory mechanism, in the hippocampus, may involve nicotinic stimulation of gamma-aminobutyric acid (GABA)ergic interneurons, resulting in decreased response to repetitive stimuli. Expression of the alpha 7 receptor is decreased in hippocampal brain tissue, dissected postmortem, from schizophrenia subjects. The P50 deficit is inherited in schizophrenia pedigrees, but it is not sufficient for disease development and thus represents a predisposition factor. Linkage analysis between the P50 deficit in multiplex schizophrenia pedigrees and deoxyribonucleic acid (DNA) markers throughout the genome yielded positive lod scores to DNA markers mapping to a region of chromosome 15 containing the alpha 7 nicotinic receptor gene. Elucidation of possible interactions of the P50 with other factors, known to be important in the etiology of the disease, is important in determining an overall pathobiology of schizophrenia.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 8873294 [PubMed - indexed for MEDLINE]

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15: Ann N Y Acad Sci. 1995 May 10;757:48-72.


Nicotinic receptor function in the mammalian central nervous system.

Albuquerque EX, Pereira EF, Castro NG, Alkondon M, Reinhardt S, Schröder H, Maelicke A.

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201, USA.

The diversity of neuronal nicotinic receptors (nAChRs) in addition to their possible involvement in such pathological conditions as Alzheimer's disease have directed our research towards the characterization of these receptors in various mammalian brain areas. Our studies have relied on electrophysiological, biochemical, and immunofluorescent techniques applied to cultured and acutely dissociated hippocampal neurons, and have been aimed at identifying the various subtypes of nAChRs expressed in the mammalian central nervous system (CNS), at defining the mechanisms by which CNS nAChR activity is modulated, and at determining the ion permeability of CNS nAChR channels. Our findings can be summarized as follows: (1) hippocampal neurons express at least three subtypes of CNS nAChRs--an alpha 7-subunit-bearing nAChR that subserves fast-inactivating, alpha-BGT-sensitive currents, which are referred to as type IA, and alpha 4 beta 2 nAChR that subserves slowly inactivating, dihydro-beta-erythroidine-sensitive currents, which are referred to as type II, and an alpha 3 beta 4 nAChR that subserves slowly inactivating, mecamylamine-sensitive currents, which are referred to as type III; (2) nicotinic agonists can activate a single type of nicotinic current in olfactory bulb neurons, that is, type IA currents; (3) alpha 7-subunit-bearing nAChR channels in the hippocampus have a brief lifetime, a high conductance, and a high Ca2+ permeability; (4) the peak amplitude of type IA currents tends to rundown with time, and this rundown can be prevented by the presence of ATP-regenerating compounds (particularly phosphocreatine) in the internal solution; (5) rectification of type IA currents is dependent on the presence of Mg2+ in the internal solution; and (6) there is an ACh-insensitive site on neuronal and nonneuronal nAChRs through which the receptor channel can be activated. These findings lay the groundwork for a better understanding of the physiological role of these receptors in synaptic transmission in the CNS.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 7611705 [PubMed - indexed for MEDLINE]

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16: Adv Neuroimmunol. 1994;4(4):339-54.


Nicotinic acetylcholine receptor: structure, function and main immunogenic region.

Mamalaki A, Tzartos SJ.

Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7719615 [PubMed - indexed for MEDLINE]

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17: Md Med J. 1992 Jul;41(7):623-31.


Progress in understanding the nicotinic acetylcholine receptor function at central and peripheral nervous system synapses through toxin interactions.

Swanson KL, Albuquerque EX.

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine.

The need to treat diseases affecting the nicotinic AChR is great, but therapeutic options are few. Through careful correlation of structure-activity relationships of AnTX analogs, we may ultimately be led to the development of diagnostic and therapeutic drugs with specific nicotinic agonist or antagonist activities in the central nervous system that would be of major importance in the treatment of Alzheimer's disease.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 1640819 [PubMed - indexed for MEDLINE]

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18: Curr Opin Neurobiol. 1992 Jun;2(3):254-62.


Diversity in primary structure and function of neuronal nicotinic acetylcholine receptor channels.

Role LW.

Department of Cell Biology and Anatomy, Columbia University College of Physicians and Surgeons, New York, New York 10032.

Neuronal nicotinic acetylcholine receptors are oligomeric protein complexes whose component subunits are each encoded by a family of homologous genes. The current challenge is to determine the functional contributions of the related subunits to the receptor-linked ion channels they compose and to uncover the physiological impact of the distinct channel classes expressed in vivo. In the past year, new approaches to the analysis of these receptors have yielded important insights into their stoichiometry, pharmacology and functional properties.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 1643408 [PubMed - indexed for MEDLINE]

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19: Ciba Found Symp. 1990;152:113-27; discussion 127-30.


Regulation of endocrine function by the nicotinic cholinergic receptor.

Fuxe K, Agnati LF, Jansson A, von Euler G, Tanganelli S, Andersson K, Eneroth P.

Department of Histology, Karolinska Institutet, Stockholm, Sweden.

One important neuroendocrine action of nicotine in the male rat is an increase in the secretion of corticosterone which is seen upon acute and acute intermittent exposure to nicotine. Tolerance develops to this action of nicotine upon chronic exposure, and in the withdrawal phase serum corticosterone levels are substantially reduced. In contrast, no significant increases of serum corticosterone levels were observed upon acute intermittent treatment with nicotine in the dioestrous rat. Available evidence indicates that corticosterone can modulate dopamine transmission in the basal ganglia via glucocorticoid receptors within the nucleus accumbens and neostriatum, and via glucocorticoid receptor immunoreactivity in nigrostriatal and mesolimbic dopamine pathways. Through concerted pre- and postsynaptic actions glucocorticoids may decrease dopamine transmission, especially that mediated by D2 receptors in these regions. In view of the hypothesis that the mesolimbic dopamine pathways mediate the euphoric effects of nicotine, the secretion of corticosterone induced by nicotine in the smoking male may substantially influence the mood elevating activity of nicotine. Thus, individual smoking habits may depend on the ability of nicotine to induce corticosterone secretion, which obviously would also vary with the degree of stress. The glucocorticoids may in a similar way influence the arousal action of nicotine because of the high number of glucocorticoid receptors present both in noradrenaline cell bodies of the locus ceruleus and within the entire cerebral cortex.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2209250 [PubMed - indexed for MEDLINE]

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20: Seikagaku. 1986 Oct;58(10):1275-91.


[Structure and function of the nicotinic acetylcholine receptor]

[Article in Japanese]

Mishina M.

Publication Types:
Review

PMID: 2434583 [PubMed - indexed for MEDLINE]
 

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