同: HC-3

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/06/23 22:42:12」(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

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

^ 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

Characteristics of nobiletin-induced effects on jejunal contractility.

Xiong YJ1, Chen DP1, Lv BC1, Liu FF1, Wang L1, Lin Y2.
Fitoterapia.Fitoterapia.2014 Apr;94:1-9. doi: 10.1016/j.fitote.2014.01.018. Epub 2014 Jan 25.
Nobiletin, a citrus polymethoxylated flavone, exhibits multiple biological properties including anti-inflammatory, anti-carcinogenic, and anti-insulin resistance effects. The present study found that nobiletin exerted significant stimulatory effects on the contractility of isolated rat jejunal segme
PMID 24468189

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. …
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 from 64 fmol/mg protein at postnatal day 7 to 142 fmol/mg protein at postnatal day 35.In nicotine−treated neonates, the development of [3H …
NAID 10008185048

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★リンクテーブル★

リンク元	「神経筋接合部」
拡張検索	「hemicholinium 3」

「神経筋接合部」

Hemicholinium-3
Systematic (IUPAC) name
	(2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium)
Identifiers
CAS Number	312-45-8
ATC code	None
PubChem	CID 9399
IUPHAR/BPS	4493
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	C24H34N2O42+
Molar 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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　　[★]

英: neuromuscular junction (K)
同: 神経筋シナプス neuromuscular synapse

神経筋接合部は軸索終末，シナプス間隙，筋細胞膜から構成される。

神経筋接合部に作用する薬物 (GPC.225)

	＋	－
神経活動電位発生		tetrodotoxin
神経活動電位発生		batrachotoxin
アセチルコリン放出	excess of Ca2+	hemicholinium
		botulinus toxin
		procaine
		Mg2+
		4-aminopyridine
		lack of Ca2+
終板電位発生	succinylcholine(suxamethonium)	curare alkaloids
終板電位発生	decamethonium	α-toxins
アセチルコリン加水分解	cholinesterase inhibitors
筋活動電位発生	veratridine	quinine
筋活動電位発生	veratridine	tetrodotoxin
筋収縮		procaine
筋収縮		dantrolene