関: hemicholinium

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/04 14:59:02」(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

No evidence for role of extracellular choline-acetyltransferase in generation of gamma oscillations in rat hippocampal slices in vitro.

Hollnagel JO1, Ul Haq R1, Behrens CJ1, Maslarova A1, Mody I2, Heinemann U3.
Neuroscience.Neuroscience.2014 Oct 16;284C:459-469. doi: 10.1016/j.neuroscience.2014.10.016. [Epub ahead of print]
Acetylcholine (ACh) is well known to induce persistent γ-oscillations in the hippocampus when applied together with physostigmine, an inhibitor of the ACh degrading enzyme acetylcholinesterase (AChE). Here we report that physostigmine alone can also dose-dependently induce γ-oscillations in rat hi
PMID 25453770

RBE4 cells are highly resistant to paraquat-induced cytotoxicity: studies on uptake and efflux mechanisms.

Vilas-Boas V1, Silva R, Guedes-de-Pinho P, Carvalho F, Bastos ML, Remião F.
Journal of applied toxicology : JAT.J Appl Toxicol.2014 Sep;34(9):1023-30. doi: 10.1002/jat.2926. Epub 2013 Sep 18.
Paraquat (PQ) is a widely used, highly toxic and non-selective contact herbicide, which has been associated with central neurotoxic effects, namely the development of Parkinson's disease, but whose effects to the blood-brain barrier (BBB) itself have rarely been studied. This work studied the mechan
PMID 24105845

Characteristics of evodiamine-exerted stimulatory effects on rat jejunal contractility.

Xiong YJ1, Chen DP, Peng JY, Wang JY, Lv BC, Liu FF, Lin Y.
Natural product research.Nat Prod Res.2014 Aug 12:1-4. [Epub ahead of print]
This study was designed to characterise the effects of evodiamine on intestinal contractility and reveal the correlated mechanisms. Evodiamine (2.5-80.0 μM) increased normal jejunal contractility and jejunal hypocontractility established under a variety of experimental conditions. Evodiamine-exert
PMID 25112370

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

「ヘミコリニウム-3」

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
Molecular 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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