Abstract
Nicotinic acetylcholine receptors (AChRs) are a family of acetylcholine-gated cation channels that form the predominant excitatory neurotransmitter receptors on muscles and nerves in the peripheral nervous system. AChRs are also expressed on neurons in lower amounts throughout the central nervous system. AChRs are even being reported on unexpected cell types such as keratinocytes. Structures of these AChRs are being determined with increasing precision, but functions of some orphan subunits are just beginning to be established. Functional roles for postsynaptic AChRs in muscle are well known, but in neurons the post-, peri-, extra-, and presynaptic roles of AChRs are just being revealed. Pathogenic roles of AChRs are being discovered in many diseases involving mechanisms ranging from mutations, to autoimmune responses, to the unknown; involving cell types ranging from muscles, to neurons, to keratinocytes; and involving signs and symptoms ranging from muscle weakness to epilepsy, to neurodegenerative disease, to psychiatric disease, to nicotine addiction. Awareness of AChR involvement in some of these diseases has provoked new interests in development of therapeutic agonists for specific AChR subtypes and the use of expressed cloned AChR subunits as possible immunotherapeutic agents. Highlights of recent developments in these areas will be briefly reviewed.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Acetylcholine / physiology*
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Alzheimer Disease / metabolism
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Anesthetics / pharmacology
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Animals
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Autoimmune Diseases / metabolism
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Cholinergic Agents / pharmacology
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Cholinergic Antagonists / pharmacology
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Epilepsy / genetics
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Epilepsy / metabolism
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Ethanol / pharmacology
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Female
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Keratinocytes / metabolism
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Male
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Models, Molecular
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Muscle Proteins / chemistry
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Muscle Proteins / classification
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Muscle Proteins / drug effects
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Muscle Proteins / genetics
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Muscle Proteins / physiology
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Myasthenia Gravis / congenital
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Myasthenia Gravis / metabolism
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / classification
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neuromuscular Junction / physiology
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Nicotine / pharmacology
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Nicotine / therapeutic use
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Parkinson Disease / metabolism
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Pregnancy
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Protein Conformation
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Receptors, Nicotinic / chemistry
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Receptors, Nicotinic / classification
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Receptors, Nicotinic / drug effects
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Receptors, Nicotinic / genetics
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Receptors, Nicotinic / physiology*
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Schizophrenia / metabolism
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Smoking / metabolism
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Torpedo
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Tourette Syndrome / drug therapy
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Tourette Syndrome / metabolism
Substances
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Anesthetics
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Cholinergic Agents
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Cholinergic Antagonists
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Muscle Proteins
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Nerve Tissue Proteins
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Receptors, Nicotinic
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Ethanol
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Nicotine
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Acetylcholine