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a neurotransmitter that is a derivative of choline; released at the ends of nerve fibers in the somatic and parasympathetic nervous systems

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アセチルコリン(神経を刺激し筋肉運動を起こす化合物)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/10 01:29:30」(JST)

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Acetylcholine (often abbreviated ACh) is an organic, polyatomic cation that acts as a neurotransmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans. It is an ester of acetic acid and choline, with chemical formula CH₃COO(CH₂)₂N⁺(CH₃)₃ and systematic name 2-acetoxy-N,N,N-trimethylethanaminium.

Acetylcholine is one of many neurotransmitters in the autonomic nervous system (ANS) and is the only neurotransmitter used in the motor division of the somatic nervous system (sensory neurons use glutamate and various peptides at their synapses). Acetylcholine is also the principal neurotransmitter in all autonomic ganglia.^{[citation needed]}

In cardiac tissue acetylcholine neurotransmission has an inhibitory effect, which lowers heart rate. However, acetylcholine also behaves as an excitatory neurotransmitter at neuromuscular junctions in skeletal muscle.^[1]

1 History
2 Function
- 2.1 In the peripheral nervous system
- 2.2 In the central nervous system
  - 2.2.1 Pathways
  - 2.2.2 Structure
  - 2.2.3 Plasticity
  - 2.2.4 Excitability and inhibition
- 2.3 Role in Decision Making
3 Synthesis and degradation
4 Receptors
- 4.1 Nicotinic
  - 4.1.1 Myasthenia gravis
- 4.2 Muscarinic
5 Drugs acting on the cholinergic system
- 5.1 ACh receptor agonists/antagonists
  - 5.1.1 Associated disorders
    - 5.1.1.1 Alzheimer's disease
  - 5.1.2 Direct acting
  - 5.1.3 Cholinesterase inhibitors
    - 5.1.3.1 Reversible
    - 5.1.3.2 Irreversible
  - 5.1.4 Reactivation of acetylcholine esterase
- 5.2 ACh receptor antagonists
  - 5.2.1 Antimuscarinic agents
  - 5.2.2 Ganglionic blockers
  - 5.2.3 Neuromuscular blockers
  - 5.2.4 Synthesis inhibitors
  - 5.2.5 Release inhibitors
  - 5.2.6 Other/uncategorized/unknown
6 Notes
7 References
8 External links

History

Acetylcholine (ACh) was first identified in 1914 by Henry Hallett Dale for its actions on heart tissue. It was confirmed as a neurotransmitter by Otto Loewi, who initially gave it the name Vagusstoff because it was released from the vagus nerve. Both received the 1936 Nobel Prize in Physiology or Medicine for their work. Acetylcholine was also the first neurotransmitter to be identified.

Function

Acetylcholine has functions both in the peripheral nervous system (PNS) and in the central nervous system (CNS) as a neuromodulator. Its receptors have very high binding constants.

In the peripheral nervous system, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system.

In the central nervous system, acetylcholine and the associated neurons form a neurotransmitter system, the cholinergic system, which tends to cause anti-excitatory actions.

In the peripheral nervous system

In the peripheral nervous system, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system. When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens ligand-gated sodium channels in the cell membrane. Sodium ions then enter the muscle cell, initiating a sequence of steps that finally produce muscle contraction. Although acetylcholine induces contraction of skeletal muscle, it acts via a different type of receptor (muscarinic) to inhibit contraction of cardiac muscle fibers.

In the autonomic nervous system, acetylcholine is released in the following sites:

all pre- and post-ganglionic parasympathetic neurons
all preganglionic sympathetic neurons
- preganglionic sympathetic fibers to suprarenal medulla, the modified sympathetic ganglion; on stimulation by acetylcholine, the suprarenal medulla releases epinephrine and norepinephrine
some postganglionic sympathetic fibers
- sudomotor neurons to sweat glands.

In the central nervous system

Micrograph of the nucleus basalis (of Meynert), which produces acetylcholine in the CNS. LFB-HE stain.

In the central nervous system, ACh has a variety of effects as a neuromodulator upon plasticity, arousal and reward. ACh has an important role in the enhancement of sensory perceptions when we wake up^[2] and in sustaining attention.^[3]

Damage to the cholinergic (acetylcholine-producing) system in the brain has been shown to be plausibly associated with the memory deficits associated with Alzheimer's disease.^[4] ACh has also been shown to promote REM sleep.^[5]

Pathways

There are three ACh pathways in the CNS.^{[citation needed]}

Pons to thalamus and cortex
Magnocellular forebrain nucleus to cortex
Septohippocampal

Structure

Acetylcholine and the associated neurons form a neurotransmitter system, the cholinergic system from the brainstem and basal forebrain that projects axons to many areas of the brain. In the brainstem it originates from the Pedunculopontine nucleus and laterodorsal tegmental nucleus collectively known as the mesopontine tegmentum area or pontomesencephalotegmental complex.^[6]^[7] In the basal forebrain, it originates from the basal optic nucleus of Meynert and medial septal nucleus:

The pontomesencephalotegmental complex acts mainly on M1 receptors in the brainstem, deep cerebellar nuclei, pontine nuclei, locus ceruleus, raphe nucleus, lateral reticular nucleus and inferior olive.^[7] It also projects to the thalamus, tectum, basal ganglia and basal forebrain.^[6]
Basal optic nucleus of Meynert acts mainly on M1 receptors in the neocortex.
Medial septal nucleus acts mainly on M1 receptors in the hippocampus and neocortex.

In addition, ACh acts as an important "internal" transmitter in the striatum, which is part of the basal ganglia. It is released by a large set of interneurons with smooth dendrites, known as tonically active neurons or TANs.

Plasticity

Excitability and inhibition

Acetylcholine also has other effects on neurons. One effect is to cause a slow depolarization^{[citation needed]} by blocking a tonically-active K⁺ current, which increases neuronal excitability. Alternatively, acetylcholine can activate non-specific cation conductances to directly excite neurons.^[8] An effect upon postsynaptic M4-muscarinic ACh receptors is to open inward-rectifier potassium ion channel (K_ir) and cause inhibition.^[9] The influence of acetylcholine on specific neuron types can be dependent upon the duration of cholinergic stimulation. For instance, transient exposure to acetylcholine (up to several seconds) can inhibit cortical pyramidal neurons via M1 type muscarinic receptors that are linked to Gq-type G-protein alpha subunits. M1 receptor activation can induce calcium-release from intracellular stores, which then activate a calcium-activated potassium conductance which inhibits pyramidal neuron firing.^[10] On the other hand, tonic M1 receptor activation is strongly excitatory. Thus, ACh acting at one type of receptor can have multiple effects on the same postsynaptic neuron, depending on the duration of receptor activation.^[11] Recent experiments in behaving animals have demonstrated that cortical neurons indeed experience both transient and persistent changes in local acetylcholine levels during cue-detection behaviors.^[12]

In the cerebral cortex, tonic ACh inhibits layer 4 medium spiny neurons, the main targets of thalamocortical inputs while exciting pyramidal cells in layers 2/3 and layer 5.^[9] This filters out weak sensory inputs in layer 4 and amplifies inputs that reach the layers 2/3 and layer L5 excitatory microcircuits. As a result, these layer-specific effects of ACh might function to improve the signal noise ratio of cortical processing.^[9] At the same time, acetylcholine acts through nicotinic receptors to excite certain groups of inhibitory interneurons in the cortex, which further dampen down cortical activity.^[13]

Role in Decision Making

One well-supported function of acetylcholine (ACh) in cortex is increased responsiveness to sensory stimuli, a form of attention. Phasic increases of ACh during visual,^[14] auditory ^[15] and somatosensory ^[16] stimulus presentations have been found to increase the firing rate of neurons in the corresponding primary sensory cortices. When cholinergic neurons in the basal forebrain are lesioned, animals' ability to detect visual signals was robustly and persistently impaired.^[17] In that same study, animals' ability to correctly reject non-target trials was not impaired, further supporting the interpretation that phasic ACh facilitates responsiveness to stimuli. Looking at ACh's effect on thalamocortical connections, a known pathway of sensory information, in vitro application of cholinergic agonist carbachol to mouse auditory cortex enhanced thalamocortical activity.^[18] In addition, Gil et al. (1997) applied a different cholinergic agonist, nicotine, and found that activity was enhanced at thalamocortical synapses.^[19] This finding provides further evidence for a facilitative role of ACh in transmission of sensory information from the thalamus to selective regions of cortex.

An additional suggested function of ACh in cortex is suppression of intracortical information transmission. Gil et al. (1997) applied the cholinergic agonist muscarine to neocortical layers and found that excitatory post-synaptic potentials between intracortical synapses were depressed.^[19] In vitro application of cholinergic agonist carbachol to mouse auditory cortex suppressed intracortical activity as well.^[18] Optical recording with a voltage-sensitive dye in rat visual cortical slices demonstrated significant suppression in intracortical spread of excitement in the presence of ACh.^[20]

Some forms of learning and plasticity in cortex appear dependent on the presence of acetylcholine. Bear et al. (1986) found that the typical synaptic remapping in striate cortex that occurs during monocular deprivation is reduced when there is a depletion of cholinergic projections to that region of cortex.^[21] Kilgard et al. (1998) found that repeated stimulation of the basal forebrain, a primary source of ACh neurons, paired with presentation of a tone at a specific frequency, resulted in remapping of the auditory cortex to better suit processing of that tone.^[22] Baskerville et al. (1996) investigated the role of ACh in experience-dependent plasticity by depleting cholinergic inputs to the barrel cortex of rats.^[23] The cholinergic depleted animals had a significantly reduced amount of whisker-pairing plasticity. Apart from the cortical areas, Crespo et al. (2006) found that the activation of nicotinic and muscarinic receptors in the nucleus accumbens is necessary for the acquisition of an appetitive task.^[24]

ACh has been implicated in the reporting of expected uncertainty in the environment ^[25] based both on the suggested functions listed above and results recorded while subjects perform a behavioral cuing task. Reaction time difference between correctly cued trials and incorrectly cued trials, called the cue validity, was found to vary inversely with ACh levels in primates with pharmacologically (e.g. Witte et al., 1997) and surgically (e.g. Voytko et al., 1994) altered levels of ACh.^[26]^[27] The result was also found in Alzheimer's disease patients (Parasuraman et al., 1992) and smokers after nicotine (an ACh agonist) consumption.^[28]^[29] The inverse covariance is consistent with the interpretation of ACh as representing expected uncertainty in the environment, further supporting this claim.

Synthesis and degradation

Acetylcholine is synthesized in certain neurons by the enzyme choline acetyltransferase from the compounds choline and acetyl-CoA. Cholinergic neurons are capable of producing ACh. An example of a central cholinergic area is the nucleus Basilis of Meynert in the basal forebrain.^{[citation needed]}

The enzyme acetylcholinesterase converts acetylcholine into the inactive metabolites choline and acetate. This enzyme is abundant in the synaptic cleft, and its role in rapidly clearing free acetylcholine from the synapse is essential for proper muscle function. Certain neurotoxins work by inhibiting acetylcholinesterase, thus leading to excess acetylcholine at the neuromuscular junction, causing paralysis of the muscles needed for breathing and stopping the beating of the heart.

Receptors

Main article: Acetylcholine receptor

There are two main classes of acetylcholine receptor (AChR), nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR). They are named for the ligands used to activate the receptors.

Nicotinic

Nicotinic AChRs are ionotropic receptors permeable to sodium, potassium, and calcium ions. They are stimulated by nicotine and acetylcholine. They are of two main types, muscle type and neuronal type. The former can be selectively blocked by curare and the latter by hexamethonium. The main location of nicotinic AChRs is on muscle end plates, autonomic ganglia (both sympathetic and parasympathetic), and in the CNS.^[30]

Myasthenia gravis

The disease myasthenia gravis, characterized by muscle weakness and fatigue, occurs when the body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits proper acetylcholine signal transmission. Over time, the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine, physostigmine, or primarily pyridostigmine) are effective in treating this disorder. They allow endogenously-released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in the gap junction.

Muscarinic

Muscarinic receptors are metabotropic, and affect neurons over a longer time frame. They are stimulated by muscarine and acetylcholine, and blocked by atropine. Muscarinic receptors are found in both the central nervous system and the peripheral nervous system, in heart, lungs, upper GI tract and sweat glands. Extracts from the plant Deadly nightshade included this compound (atropine), and the blocking of the muscarinic AChRs increases pupil size as used for attractiveness in many European cultures in the past. Now, ACh is sometimes used during cataract surgery to produce rapid constriction of the pupil. It must be administered intraocularly because corneal cholinesterase metabolizes topically-administered ACh before it can diffuse into the eye. It is sold by the trade name Miochol-E (CIBA Vision). Similar drugs are used to induce mydriasis (dilation of the pupil), in cardiopulmonary resuscitation and many other situations.

Drugs acting on the cholinergic system

Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Drugs acting on the acetylcholine system are either agonists to the receptors, stimulating the system, or antagonists, inhibiting it.

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

ACh receptor agonists/antagonists

Acetylcholine receptor agonists and antagonists can either have an effect directly on the receptors or exert their effects indirectly, e.g., by affecting the enzyme acetylcholinesterase, which degrades the receptor ligand. Agonists increase the level of receptor activation, antagonists reduce it.

Associated disorders

ACh Receptor Agonists are used to treat myasthenia gravis and Alzheimer's disease.

Alzheimer's disease

Since α4β2 AchRs are reduced in Alzheimer's disease, drugs that inhibit acetylcholinesterase, e.g. galantamine hydrobromide (a competitive and reversible cholinesterase inhibitor), are commonly used in its treatment.

Direct acting

These are drugs that mimic acetylcholine on the receptor. In low doses, they stimulate the receptors, in high they numb them due to depolarisation block.

Acetyl l-carnitine^[31]
Acetylcholine itself
Bethanechol
Carbachol

Cevimeline
Muscarine
Nicotine

Pilocarpine
Suberylcholine
Suxamethonium

Cholinesterase inhibitors

Main article: Cholinesterase inhibitors

Most indirect acting ACh receptor agonists work by inhibiting the enzyme acetylcholinesterase. The resulting accumulation of acetylcholine causes continuous stimulation of the muscles, glands, and central nervous system.

They are examples of enzyme inhibitors, and increase the action of acetylcholine by delaying its degradation; some have been used as nerve agents (Sarin and VX nerve gas) or pesticides (organophosphates and the carbamates). In clinical use, they are administered to reverse the action of muscle relaxants, to treat myasthenia gravis, and to treat symptoms of Alzheimer's disease (rivastigmine, which increases cholinergic activity in the brain).

Reversible

The following substances reversibly inhibit the enzyme acetylcholinesterase (which breaks down acetylcholine), thereby increasing acetylcholine levels.^{[citation needed]}

Many medications in Alzheimer's disease
- Donepezil
- Galantamine
- Rivastigmine
- Tacrine
Edrophonium (differs myasthenic and cholinergic crisis)
Neostigmine (commonly used to reverse the effect of neuromuscular blockers used in anaesthesia, or less often in myasthenia gravis)
Physostigmine (in glaucoma and anticholinergic drug overdoses)
Pyridostigmine (in myasthenia gravis)
Carbamate insecticides (e.g., Aldicarb)
Huperzine A

Irreversible

Semi-permanently inhibit the enzyme acetylcholinesterase.

Echothiophate
Isofluorophate
Organophosphate Insecticides (Malathion, Parathion, Azinphos methyl, Chlorpyrifos, among others)
Organophosphate-containing nerve agents (e.g., Sarin, VX)

Victims of organophosphate-containing nerve agents commonly die of suffocation as they cannot relax their diaphragm.

Reactivation of acetylcholine esterase

Pralidoxime

ACh receptor antagonists

Antimuscarinic agents

Atropine
Ipratropium
Scopolamine
Tiotropium
Diphenhydramine

Ganglionic blockers

Mecamylamine
Hexamethonium
Trimethaphan
Bupropion
Dextromethorphan

Neuromuscular blockers

Atracurium
Cisatracurium
Doxacurium
Metocurine

Mivacurium
Pancuronium
Rocuronium
Succinylcholine

Tubocurarine
Vecuronium
Hemicholine

Synthesis inhibitors

Organic mercurial compounds, such as methylmercury, have a high affinity for sulfhydryl groups, which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function.

Release inhibitors

Botulin acts by suppressing the release of acetylcholine; where the venom from a black widow spider (alpha-latrotoxin) has the reverse effect. ACh inhibition causes paralysis. When bitten by a black widow spider, one experiences the wastage of ACh supplies and the muscles begin to contract. If and when the supply is depleted paralysis occurs.

Other/uncategorized/unknown

Surugatoxin

Notes

^ Campbell, N. A.; Reece, J. B. (2002). "48". Biology (6th ed.). San Francisco, CA: Pearson Education, Inc.. pp. 1037. ISBN 0-8053-6624-5.
^ Jones, BE (2005). "From waking to sleeping: neuronal and chemical substrates". Trends in pharmacological sciences 26 (11): 578–86. doi:10.1016/j.tips.2005.09.009. PMID 16183137.
^ Himmelheber, AM; Sarter, M; Bruno, JP (2000). "Increases in cortical acetylcholine release during sustained attention performance in rats". Brain research. Cognitive brain research 9 (3): 313–25. doi:10.1016/S0926-6410(00)00012-4. PMID 10808142.
^ http://www.biopsychiatry.com/alzheim.htm
^ Platt, Bettina; Riedel, Gernot (2011). "The cholinergic system, EEG and sleep". Behavioural Brain Research 221 (2): 499–504. doi:10.1016/j.bbr.2011.01.017. PMID 21238497.
^ ^a ^b Woolf, NJ; Butcher, LL (1986). "Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain". Brain Research Bulletin 16 (5): 603–37. doi:10.1016/0361-9230(86)90134-6. PMID 3742247.
^ ^a ^b Woolf, NJ; Butcher, LL (1989). "Cholinergic systems in the rat brain: IV. Descending projections of the pontomesencephalic tegmentum". Brain Research Bulletin 23 (6): 519–40. doi:10.1016/0361-9230(89)90197-4. PMID 2611694.
^ Haj-Dahmane, S; Andrade, R (1996). "Muscarinic activation of a voltage-dependent cation nonselective current in rat association cortex". Journal of Neuroscience 16 (12): 3848–61. PMID 8656279.
^ ^a ^b ^c Eggermann, E; Feldmeyer, D (2009). "Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4". Proceedings of the National Academy of Sciences of the United States of America 106 (28): 11753–8. doi:10.1073/pnas.0810062106. PMC 2710689. PMID 19564614. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2710689/.
^ Gulledge, AT; Stuart, GJ (2005). "Cholinergic inhibition of neocortical pyramidal neurons". Journal of Neuroscience 25 (44): 10308–20. doi:10.1523/JNEUROSCI.2697-05.2005. PMID 16267239.
^ Gulledge, AT; Bucci, DJ; Zhang, SS; Matsui, M; Yeh, HH (2009). "M1 Receptors Mediate Cholinergic Modulation of Excitability in Neocortical Pyramidal Neurons". Journal of Neuroscience 29 (31): 9888–902. doi:10.1523/JNEUROSCI.1366-09.2009. PMC 2745329. PMID 19657040. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2745329/.
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^ Spehlmann R, Daniels JC, Smathers CC (1971). "Acetylcholine and the synaptic transmission of specific impulses to the visual cortex". Brain 94 (1): 125–38. PMID 4324030. http://brain.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=4324030.
^ Foote SL, Freedman R, Oliver AP (March 1975). "Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex". Brain Res. 86 (2): 229–42. doi:10.1016/0006-8993(75)90699-X. PMID 234774. http://linkinghub.elsevier.com/retrieve/pii/0006-8993(75)90699-X.
^ Stone TW (September 1972). "Cholinergic mechanisms in the rat somatosensory cerebral cortex". J. Physiol. (Lond.) 225 (2): 485–99. PMC 1331117. PMID 5074408. http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=5074408.
^ McGaughy J, Kaiser T, Sarter M (April 1996). "Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density". Behav. Neurosci. 110 (2): 247–65. PMID 8731052. http://content.apa.org/pubmed/bne/110/2/247.
^ ^a ^b Hsieh CY, Cruikshank SJ, Metherate R (October 2000). "Differential modulation of auditory thalamocortical and intracortical synaptic transmission by cholinergic agonist". Brain Res. 880 (1-2): 51–64. doi:10.1016/S0006-8993(00)02766-9. PMID 11032989. http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(00)02766-9.
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^ Bear MF, Singer W (1986). "Modulation of visual cortical plasticity by acetylcholine and noradrenaline". Nature 320 (6058): 172–6. doi:10.1038/320172a0. PMID 3005879.
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^ Baskerville KA, Schweitzer JB, Herron P (October 1997). "Effects of cholinergic depletion on experience-dependent plasticity in the cortex of the rat". Neuroscience 80 (4): 1159–69. doi:10.1016/S0306-4522(97)00064-X. PMID 9284068. http://linkinghub.elsevier.com/retrieve/pii/S030645229700064X.
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^ Yu & Dayan 2005
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References

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English Journal

An eco-friendly, simple, and sensitive fluorescence biosensor for the detection of choline and acetylcholine based on C-dots and the Fenton reaction.

Wei J, Ren J, Liu J, Meng X, Ren X, Chen Z, Tang F.Author information Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No. 29, Zhongguancun East Road, Haidian District, Beijing 100190, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.AbstractA simple and novel method is proposed for the preparation of Carbon dots (C-dots) with excellent properties. We firstly demonstrated that the fluorescence of C-dots decreased apparently in the presence of H2O2 and Fe(2+). Based on the this finding, C-dots are successfully adopted as probes for the detection of H2O2. After the experimental conditions are optimized, the limit of detection (LOD) for H2O2 is found to be 0.1μM. Furthermore, we established an eco-friendly, simple and sensitive biosensor for the detection of choline and acetylcholine (ACh) based on the detection of H2O2 using C-dots as probes. The detection limit for choline is 0.1μM and the linear range is 0.1-40μM. The detection limit for ACh is found to be 0.5μM and the linear range is 0.5-60μM. The excellent performance of the proposed biosensor shows that this method possesses the potential for practical application.
Biosensors & bioelectronics.Biosens Bioelectron.2014 Feb 15;52:304-9. doi: 10.1016/j.bios.2013.09.006. Epub 2013 Sep 14.
A simple and novel method is proposed for the preparation of Carbon dots (C-dots) with excellent properties. We firstly demonstrated that the fluorescence of C-dots decreased apparently in the presence of H2O2 and Fe(2+). Based on the this finding, C-dots are successfully adopted as probes for the d
PMID 24080209

Serotonin-immunoreactive sensory neurons in the antenna of the cockroach Periplaneta americana.

Watanabe H, Shimohigashi M, Yokohari F.Author information Division of Biology, Department of Earth System Science, Fukuoka University, Fukuoka, Japan.AbstractThe antennae of insects contain a vast array of sensory neurons that process olfactory, gustatory, mechanosensory, hygrosensory, and thermosensory information. Except those with multimodal functions, most sensory neurons use acetylcholine as a neurotransmitter. Using immunohistochemistry combined with retrograde staining of antennal sensory neurons in the cockroach Periplaneta americana, we found serotonin-immunoreactive sensory neurons in the antenna. These were selectively distributed in chaetic and scolopidial sensilla and in the scape, the pedicel, and first 15 segments of the flagellum. In a chaetic sensillum, A single serotonin-immunoreactive sensory neuron cohabited with up to four serotonin-negative sensory neurons. Based on their morphological features, serotonin-immunopositive and -negative sensory neurons might process mechanosensory and contact chemosensory modalities, respectively. Scolopidial sensilla constitute the chordotonal and Johnston's organs within the pedicel and process antennal vibrations. Immunoelectron microscopy clearly revealed that serotonin-immunoreactivities selectively localize to a specific type of mechanosensory neuron, called type 1 sensory neuron. In a chordotonal scolopidial sensillum, a serotonin-immunoreactive type 1 neuron always paired with a serotonin-negative type 1 neuron. Conversely, serotonin-immunopositive and -negative type 1 neurons were randomly distributed in Johnston's organ. In the deutocerebrum, serotonin-immunoreactive sensory neuron axons formed three different sensory tracts and those from distinct types of sensilla terminated in distinct brain regions. Our findings indicate that a biogenic amine, serotonin, may act as a neurotransmitter in peripheral mechanosensory neurons. J. Comp. Neurol. 522:414-434, 2014. © 2013 Wiley Periodicals, Inc.
The Journal of comparative neurology.J Comp Neurol.2014 Feb;522(2):414-34. doi: 10.1002/cne.23419.
The antennae of insects contain a vast array of sensory neurons that process olfactory, gustatory, mechanosensory, hygrosensory, and thermosensory information. Except those with multimodal functions, most sensory neurons use acetylcholine as a neurotransmitter. Using immunohistochemistry combined wi
PMID 23852943

Pulmonary exposure to particles from diesel exhaust, urban dust or single-walled carbon nanotubes and oxidatively damaged DNA and vascular function in apoE(-/-) mice.

Vesterdal LK, Jantzen K, Sheykhzade M, Roursgaard M, Folkmann JK, Loft S, Møller P.Author information Department of Public Health, Section of Environmental Health, University of Copenhagen , Copenhagen , Denmark.AbstractAbstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells and acellullarly, whereas the exposure to urban dust did not generate ROS. The apoE(-/-) mice, which were exposed twice to 0.5 mg/kg of the particles by intratracheal (i.t.) instillation, had unaltered acetylcholine-elicited vasorelaxation in aorta segments. There was unaltered pulmonary expression level of Vcam-1, Icam-1, Hmox-1 and Ogg1. The levels of oxidatively damaged DNA were unchanged in lung tissue. The exposure to SWCNT significantly increased the expression of Ccl-2 in the lung tissue of the mice. The exposure to DEP and SWCNT was associated with elevated ROS production in cultured cells, whereas i.t. instillation of the same particles had no effect on biomarkers of pulmonary oxidative stress and dilatory dysfunction in the aorta.
Nanotoxicology.Nanotoxicology.2014 Feb;8:61-71. doi: 10.3109/17435390.2012.750385. Epub 2012 Dec 11.
Abstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells and acellull
PMID 23148895

Protective effect of Millettia pulchra polysaccharide on cognitive impairment induced by d-galactose in mice.

Lin X, Huang Z, Chen X, Rong Y, Zhang S, Jiao Y, Huang Q, Huang R.Author information Guangxi Medical University, Nanning, Guangxi 530021, China.AbstractA polysaccharide (PMP) was isolated from Millettia pulchra and purified by DEAE-cellulose and Sephadex G-75 chromatography. The results showed that PMP was composed of d-glucose and d-arabinose in a molar ratio of 90.79% and 9.21%, with an average molecular weight of about 14,301Da. Furthermore, the effect of PMP on cognitive impairment induced by d-galactose in mice was evaluated. Treatment with PMP significantly reversed d-galactose-induced learning and memory impairments, as measured by behavioral tests. One of the potential mechanisms of this action was to reduce oxidative stress and suppress inflammatory responses. Furthermore, our results also showed that PMP markedly reduced the content and deposition of β-amyloid peptide, improved the dysfunction of synaptic plasticity, increased the levels of acetylcholine, but decreased cholinesterase activity. These results suggest that PMP exerts an effective protection against d-galactose-induced cognitive impairment, and PMP may be a major bioactive ingredient in M. pulchra.
Carbohydrate polymers.Carbohydr Polym.2014 Jan 30;101:533-43. doi: 10.1016/j.carbpol.2013.09.037. Epub 2013 Sep 23.
A polysaccharide (PMP) was isolated from Millettia pulchra and purified by DEAE-cellulose and Sephadex G-75 chromatography. The results showed that PMP was composed of d-glucose and d-arabinose in a molar ratio of 90.79% and 9.21%, with an average molecular weight of about 14,301Da. Furthermore, the
PMID 24299809

Japanese Journal

Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

Haga Kazuko,Kruse Andrew C.,Asada Hidetsugu,Yurugi-Kobayashi Takami,Shiroishi Mitsunori,Zhang Cheng,Weis William I.,Okada Tetsuji,Kobilka Brian K.,Haga Tatsuya,Kobayashi Takuya
Nature, 2012-01-25
… 京都大学プレスリリース.2012-01-26.The parasympathetic branch of the autonomic nervous system regulates the activity ofmultiple organ systems.Muscarinic receptorsare G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves1–5. …
NAID 120003752107

The 3rd International Symposium on Non-neuronal Acetylcholine (フローニンゲン, オランダ)に出席して

川島紘一郎
日本薬理學雜誌 = Folia pharmacologica Japonica 138(5), 223, 2011-11-01
NAID 10029896446

Elevated Cystatin C Levels Predict the Incidence of Vasospastic Angina

FUNAYAMA Akira,WATANABE Tetsu,TAMABUCHI Toshiaki,OTAKI Yoichiro,NETSU Shunsuke,HASEGAWA Hiromasa,HONDA Shintaro,ISHINO Mitsunori,ARIMOTO Takanori,TAKAHASHI Hiroki,SHISHIDO Tetsuro,MIYAMOTO Takuya,NITOBE Joji,KUBOTA Isao
Circulation journal : official journal of the Japanese Circulation Society 75(10), 2439-2444, 2011-09-25
… VSA was evoked in 59 patients by a vasospasm provocation test with administration of acetylcholine into the coronary arteries. …
NAID 10029459648

Related Pictures

★リンクテーブル★

リンク元	「アセチルコリン」「コリン」「acetylcholine chloride」「ACh」
拡張検索	「vesicular acetylcholine transporter」「acetylcholine受容体」「acetylcholine receptor antibody」「acetylcholine receptor」

「アセチルコリン」

Acetylcholine
Abbreviation	ACh
Sources	many
Targets	many
Receptors	nicotinic; muscarinic
Agonists	nicotine, muscarine
Antagonists	curare, atropine
Precursor	choline
Synthesizing enzyme	Choline acetyltransferase (ChAT)
Metabolizing enzyme	Acetylcholinesterase (AChE)

Acetylcholine
	IUPAC name 2-Acetoxy-N,N,N-trimethylethanaminium
Identifiers
Abbreviations	ACh
CAS number	51-84-3
PubChem	187
ChemSpider	182
UNII	N9YNS0M02X
EC number	200-128-9
DrugBank	EXPT00412
KEGG	C01996
MeSH	Acetylcholine
ChEBI	CHEBI:15355
ChEMBL	CHEMBL667
IUPHAR ligand	294
Beilstein Reference	1764436
Gmelin Reference	326108
3DMet	B00379
Jmol-3D images	Image 1
	SMILES CC(=O)OCC[N+](C)(C)C ;
	InChI InChI=1S/C7H16NO2/c1-7(9)10-6-5-8(2,3)4/h5-6H2,1-4H3/q+1 ; Key: OIPILFWXSMYKGL-UHFFFAOYSA-N InChI=1/C7H16NO2/c1-7(9)10-6-5-8(2,3)4/h5-6H2,1-4H3/q+1; Key: OIPILFWXSMYKGL-UHFFFAOYAY ;
Properties
Molecular formula	C7NH16O+; 2
Molar mass	146.2074 g mol-1
Pharmacology
Elimination; half-life	2 min
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references