WordNet

a neurotransmitter that is a derivative of choline; released at the ends of nerve fibers in the somatic and parasympathetic nervous systems
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

アセチルコリン(神経を刺激し筋肉運動を起こす化合物)
=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/31 09:44:52」(JST)

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Acetylcholine

An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.

Classification

Like other transmembrane receptors, acetylcholine receptors are classified according to their "pharmacology," or according to their relative affinities and sensitivities to different molecules. Although all acetylcholine receptors, by definition, respond to acetylcholine, they respond to other molecules as well.

nicotinic acetylcholine receptors (nAChR, also known as "ionotropic" acetylcholine receptors) are particularly responsive to nicotine. The nicotine ACh receptor is also a Na+ and K+ ion channel
muscarinic acetylcholine receptors (mAChR, also known as "metabotropic" acetylcholine receptors) are particularly responsive to muscarine.

Nicotinic and muscarinic are two main kinds of "cholinergic" receptors.

Receptor types

Molecular biology has shown that the nicotinic and muscarinic receptors belong to distinct protein superfamilies.

ACh and its receptors
Drug	Nm	Nn	M1	M2	M3
ACh, Charbacol, AChEi (Psysostigmine, Galantamine, Neostigmine, Pyridostigmine)	+	+	+	+	+
Nicotine, Varenicline	+	+
Succinylcholine	+/-
Atracurium, Vecuronium, Tubocurarine, Pancuronium	-
Epibatidine, DMPP		+
Trimethaphan, Mecamylamine, Bupropion, Dextromethophan, Hexamethonium		-
Muscarine, Methacholine, Oxotremorine, Bethanechol, Pilocarpine			+	+	+
Atropine, Tolterodine, Oxybutynin			-	-	-
Vedaclidine, Talsaclidine, Xanomeline, Ipatropium			+
Pirenzepine, Telenzepine			-
Methoctramin				-
Darifenacin, 4-DAMP, Darifenacin, Solifenacin					-

nAChR

Main article: Nicotinic acetylcholine receptors

The nAChRs are ligand-gated ion channels, and, like other members of the "cys-loop" ligand-gated ion channel superfamily, are composed of five protein subunits symmetrically arranged like staves around a barrel. The subunit composition is highly variable across different tissues. Each subunit contains four regions which span the membrane and consist of approximately 20 amino acids. Region II which sits closest to the pore lumen, forms the pore lining. ^[1]

Binding of acetylcholine to the N termini of each of the two alpha subunits results in the 15° rotation of all M2 helices.^[2] The cytoplasm side of the nAChR receptor has rings of high negative charge that determine the specific cation specificity of the receptor and remove the hydration shell often formed by ions in aqueous solution. In the intermediate region of the receptor, within the pore lumen, valine and leucine residues (Val 255 and Leu 251) define a hydrophobic region through which the dehydrated ion must pass.^[3]

The nAChR is found at the edges of junctional folds at the neuromuscular junction on the postsynaptic side; it is activated by acetylcholine release across the synapse. The diffusion of Na⁺ and K⁺ across the receptor causes depolarization, the end-plate potential, that opens voltage-gated sodium channels, which allows for firing of the action potential and potentially muscular contraction.

mAChR

Main article: Muscarinic acetylcholine receptors

In contrast, the mAChRs are not ion channels, but belong instead to the superfamily of G-protein-coupled receptors that activate other ionic channels via a second messenger cascade. The muscarine cholinergic receptor activates a G protein when bound to extracellular ACh. The alpha subunit of the Gprotein deactivates adenylate cyclase while the betagamma subunit activates the Kchannels and therefore hyperpolarise the cell. This causes a decrease in cardiac activity.

Role in health and disease

Nicotinic acetylcholine receptors can be blocked by curare, hexamethonium and toxins present in the venoms of snakes and shellfishes, like α-bungarotoxin. Drugs such as the neuromuscular blocking agents bind reversibly to the nicotinic receptors in the neuromuscular junction and are used routinely in anaesthesia.

Nicotinic receptors are the primary mediator of the effects of nicotine. In myasthenia gravis, the receptor at NMJ is targeted by antibodies, leading to muscle weakness. Muscarinic acetylcholine receptors can be blocked by the drugs atropine and scopolamine.

External links

Acetylcholine receptor: PMAP The Proteolysis Map-animation
Acetylcholine+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
Acetlycholine Receptor: Molecule of The Month by David Goodsell

References

^ Pohanka, M (2012). "Alpha7 Nicotinic Acetylcholine Receptor Is a Target in Pharmacology and Toxicology". International Journal of Molecular Sciences 13 (2): 2219–2238. doi:10.3390/ijms13022219. PMC 3292018. PMID 22408449. http://www.mdpi.com/1422-0067/13/2/2219.
^ Doyle DA (2004). "Structural changes during ion channel gating". Trends Neurosci. 27 (6): 298–302. doi:10.1016/j.tins.2004.04.004. PMID 15165732.
^ Miyazawa A, Fujiyoshi Y, Unwin N (2003). "Structure and gating mechanism of the acetylcholine receptor pore". Nature 423 (6943): 949–55. doi:10.1038/nature01748. PMID 12827192.

UpToDate Contents

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1. 慢性閉塞性肺疾患（COPD）における抗コリン療法の役割 role of anticholinergic therapy in copd
2. 神経筋接合部に作用する毒素の概要 overview of neuromuscular junction toxins
3. 重症筋無力症の診断 diagnosis of myasthenia gravis
4. 抗コリン剤中毒 anticholinergic poisoning
5. ニコチンの心血管系への影響 cardiovascular effects of nicotine

English Journal

Role of cholinergic-muscarinic receptors in visual discrimination performance of rats: Importance of stimulus load.

Tsui CK, Dringenberg HC.SourceDepartment of Psychology, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Behavioural brain research.Behav Brain Res.2013 Feb 1;238:23-9. doi: 10.1016/j.bbr.2012.10.005. Epub 2012 Oct 16.
Central cholinergic transmission has long been implicated in various cognitive processes, including memory acquisition, consolidation, and attentional processes. Here, we examined the role of muscarinic receptors in visual discrimination performance under conditions of altered visual information ava
PMID 23078949

Impairment of the septal cholinergic neurons in MPTP-treated A30P α-synuclein mice.

Szegő EM, Outeiro TF, Kermer P, Schulz JB.SourceDepartment of NeuroDegeneration and Restorative Research, Georg-August University, DFG Research Center, Molecular Physiology of the Brain (CMPB), Göttingen, Germany. Electronic address: eszego@uni-goettingen.de.
Neurobiology of aging.Neurobiol Aging.2013 Feb;34(2):589-601. doi: 10.1016/j.neurobiolaging.2012.04.012. Epub 2012 May 11.
Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of
PMID 22579457

Japanese Journal

Thymus histology and concomitant autoimmune diseases in Japanese patients with muscle-specific receptor tyrosine kinase-antibody-positive myasthenia gravis

Nakata Ruka,Motomura Masakatsu,Masuda Tomoko,Shiraishi Hirokazu,Tokuda Masahiro,Fukuda Taku,Ando Takao,Yoshimura Toshiro,Tsujihata Mitsuhiro,Kawakami Atsushi
European Journal of Neurology 20(9), 1272-1276, 2013-09-00
… Background and purpose: The differences in the characteristics of thymus histology, coexisting autoimmune diseases and related autoantibodies between anti-muscle-specific receptor tyrosine kinase (MuSK)-antibody (Ab)-positive myasthenia gravis (MG) patients, and anti-acetylcholine receptor (AChR)-Ab-positive MG patients are not clearly defined. …
NAID 120005328277

重症筋無力症における味覚障害と抗電位依存性カリウムチャンネル(Kv)1.4抗体

蒲澤千昌,清水優子,鈴木重明,内山真一郎
東京女子医科大学雑誌 83(4), 242-248, 2013-08-25
緒言:近年、重症筋無力症(MG)患者に新規抗体が報告され、その一つである抗電位依存性カリウムチャンネル(Kv)1.4抗体陽性のMG患者では重症度と相関すると言われている.MGの非運動性障害の一つに味覚障害が報告されているが、有症率や発症機序は不明である.今回、多施設共同研究によりMGの味覚障害を検討した. 対象および方法:2010年5月から9月に多施設共同研究East Japan MG study …
NAID 110009610660

Autoantibody-induced internalization of nicotinic acetylcholine receptor α3 subunit exogenously expressed in human embryonic kidney cells

Kobayashi Shota,Yokoyama Shigeru,Maruta Takahiro,Negami Masako,Muroyama Akiko,Mitsumoto Yasuhide,Iwasa Kazuo,Yamada Masahito,Yoshikawa Hiroaki
Journal of Neuroimmunology 257(1-2), 102-106, 2013-04-15
… Autoantibody against nicotinic acetylcholine receptor (nAChR) α3 subunit has been implicated in the pathogenesis of paraneoplastic neurological syndrome. …
NAID 120005253252

Related Pictures

★リンクテーブル★

リンク元	「アセチルコリン受容体」「cholinergic receptor」「acetylcholine受容体」「acetylcholineレセプター」「アセチルコリンレセプター」
拡張検索	「muscarinic acetylcholine receptor」「acetylcholine receptor antibody」
関連記事	「acetylcholine」

「アセチルコリン受容体」

　　[★]

英: acetylcholine receptor, AChR
同: コリン作動性受容体 (SPC.134)、Ach受容体、アセチルコリン作動性受容体
関: アドレナリン受容体、アセチルコリン

アセチルコリン受容体 (SP.412)

アセチルコリン受容体			作動薬	遮断薬	存在部位	作用
ニコチン性受容体	イオンチャネル型受容体	N_N	ジメチルフェニルピペラジニウム	トリメタファン	自律神経節	節後細胞脱分極（fast EPSP発生）
			ニコチン	ヘキサメソニウム	副腎髄質	カテコールアミン分泌促進
ムスカリン性受容体	Gタンパク共役型受容体	M₁	オキソトレモリン	ピレンゼピン	自律神経節	節後細胞脱分極（slow EPSP発生）
			ムスカリン	アトロピン
		M₂	ムスカリン	トリピトラミン	心臓	心拍数，伝導速度，心房収縮力低下
				アトロピン
		M₃	ムスカリン	ダリフェナシン	平滑筋	収縮
				アトロピン	分泌腺	分泌促進