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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/22 09:48:21」(JST)

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Hemicholinium-3 (HC3), also known as hemicholine, is a drug which blocks the reuptake of choline by the high-affinity choline transporter (ChT; encoded in humans by the gene SLC5A7) at the presynapse. The reuptake of choline is the rate limiting step in the synthesis of acetylcholine; hence, hemicholinium-3 decreases the synthesis of acetylcholine. It is therefore classified as an indirect acetylcholine antagonist.^[1]

Acetylcholine is synthesized from choline and a donated acetyl group from acetyl-CoA, by the action of choline acetyltransferase (ChAT). Thus, decreasing the amount of choline available to a neuron will decrease the amount of acetylcholine produced. Neurons affected by hemicholinium-3 must rely on the transport of choline from the soma (cell body), rather than relying on reuptake of choline from the synaptic cleft.

Effects[edit]

Hemicholinium-3 has no clinical use, but is frequently used as a research tool in animal and in vitro experiments. The clinical use is limited since it prevents uptake into the cell which is not a rate limiting factor under normal, physiological frequencies of activation. This type of inhibition only becomes apparent at excessively high firing rates, whereby the uptake of choline into the nerve terminal as a rate limiting factor becomes apparent.

Hemoicholinium-3 produces a decrease in acetylcholine content in the nerve terminal and as a consequence results in a decrease in acetylcholine transmission. Since acetylcholine normally binds to nicotinic and muscarinic receptors in synapses, a decrease in acetylcholine would cause a decrease in nicotinic and muscarinic pharmacology.

References[edit]

^ Carlson, Neil R. (2007). Physiology of Behavior (9th ed.). Boston: Pearson Education, Inc. p. 117. ISBN 0-205-46724-5.

English Journal

Cigarette smoke alters non-neuronal cholinergic system components inducing MUC5AC production in the H292 cell line.

Montalbano AM1, Albano GD2, Anzalone G1, Bonanno A1, Riccobono L1, Sano CD1, Gagliardo R1, Siena L1, Pieper MP3, Gjomarkaj M1, Profita M4.
European journal of pharmacology.Eur J Pharmacol.2014 May 2. pii: S0014-2999(14)00307-0. doi: 10.1016/j.ejphar.2014.04.022. [Epub ahead of print]
Cigarette smoke extract (CSE) affects the expression of Choline Acetyl-Transferase (ChAT), muscarinic acetylcholine receptors, and mucin production in bronchial epithelial cells. Mucin 5AC (MUC5AC), muscarinic acetylcholine receptor M3, ChAT expression, acetylcholine levels and acetylcholine binding
PMID 24797786

Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients.

Profita M1, Albano GD2, Riccobono L3, Di Sano C3, Montalbano AM3, Gagliardo R3, Anzalone G3, Bonanno A3, Pieper MP4, Gjomarkaj M3.
Immunobiology.Immunobiology.2014 May;219(5):392-401. doi: 10.1016/j.imbio.2014.01.004. Epub 2014 Jan 25.
T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22,
PMID 24529390

Japanese Journal

コリンおよびコリントランスポーターの生理機能(<特集>ビタミン・バイオファクターのトランスポーター[I])

稲津正人
ビタミン 84(8), 365-375, 2010-08-25
… CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 (HC-3) and essentially display characteristics of specialized transporters for targeted choline metabolism. … CHT1 is a Na^+-dependent co-transporter that is highly sensitive to the choline analogue, HC-3, and is thought to be part of the rate-limiting step in acetylcholine synthesis. …
NAID 110007682293

Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice

FERGUSON SM
Proc Natl Acad Sci USA 101, 8762-8767, 2004
NAID 80016736181

Effects of Perinatal Nicotine Exposure on Development of [^3H]Hemicholinium-3 Binding Sites in Rat Neonate Brain

Zhu Jun,Taniguchi Takanobu,Tanaka Takashi [他],SUZUKI Fumiko,MURAMATSU Ikunobu
The Japanese journal of pharmacology 84(1), 32-35, 2000-09-01
… this study, [3H]hemicholinium−3([3H]HC−3)binding, which labels the presynaptic high affinity−choline transport sites, was examined in two brain regions, cerebral cortex and midbrain, of nicotine−treated and −untreated rat neonates.In nicotine−untreated neonates, [3H]HC−3 binding sites of cerebral cortex increased …
NAID 10008185048

Related Pictures

hemicholinium-3-sensitive choline Amino Acid Sequence of Siamese Cobra Cholinergic Drugs II Pharmacology of Neuromuscular Transmission HC- 3 : Hemicholinium - 3 ; Agents that alter the Neuromuscular

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リンク元	「ヘミコリニウム」
関連記事	「hemicholinium 3」「hemicholinium」

「ヘミコリニウム」

Hemicholinium-3
Systematic (IUPAC) name
	(2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium)
Clinical data
Legal status	?
Identifiers
CAS number	312-45-8
ATC code	None
PubChem	CID 9399
ChemSpider	9029
ChEMBL	CHEMBL268697
Synonyms	2-[4-[4-(2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl)phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol
Chemical data
Formula	C24H34N2O4 +2
Mol. mass	414.538 g/mol
	SMILES [Br-].[Br-].OC1(OCC[N+](C)(C)C1)c2ccc(cc2)c3ccc(cc3)C4(O)OCC[N+](C)(C)C4;
	InChI InChI=1S/C24H34N2O4.2BrH/c1-25(2)13-15-29-23(27,17-25)21-9-5-19(6-10-21)20-7-11-22(12-8-20)24(28)18-26(3,4)14-16-30-24;;/h5-12,27-28H,13-18H2,1-4H3;2*1H/q+2;;/p-2 ; Key:OPYKHUMNFAMIBL-UHFFFAOYSA-L ;
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