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a(CHEBI:acetylcholine)

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Entity

Name
acetylcholine
Namespace
chebi
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

Appears in Networks 15

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer's disease and schizophrenia. v1.0.0

This file encodes the article Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer’s disease and schizophrenia by Choi et al, 2014

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System v1.0.0

Alzheimer's Disease: Targeting the Cholinergic System v1.0.0

Interplay of neurotransmitters in Alzheimer's disease v1.0.0

M1 muscarinic acetylcholine receptor in Alzheimer’s disease v1.0.0

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses v1.0.0

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications v1.0.0

Nicotinic Receptor Abnormalities of Alzheimer’s Disease: Therapeutic Implications v1.0.0

B-973, a novel piperazine positive allosteric modulator of the α7 nicotinic acetylcholine receptor v1.0.0

Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system v1.0.0

This document contains the curation of the review article Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system by Taly et al. 2009

Naturally-expressed nicotinic acetylcholine receptor subtypes v1.0.0

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

In-Edges 64

complex(a(CHEBI:acetylcholine), p(FPLX:CHRM)) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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bp(GO:signaling) association a(CHEBI:acetylcholine) View Subject | View Object

From the time of its discovery in 1914 by Henry H. Dale (109) and Otto Loewi (283) (the two shared the Nobel Prize in Physiology and Medicine in 1936) as an agent that decreases heart rate, ACh was recognized as an endogenous signaling compound, synthesized from choline and acetyl-CoA, through the action of choline acetyltransferase, that alters cell function. PubMed:19126755

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rxn(reactants(a(CHEBI:"acetyl-CoA"), a(CHEBI:choline)), products(a(CHEBI:acetylcholine))) hasProduct a(CHEBI:acetylcholine) View Subject | View Object

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a(CHEBI:nicotine) increases a(CHEBI:acetylcholine) View Subject | View Object

It is now well established that exposure to nicotine results in increased expression of nAChRs in brain and in cultured cells (for review, see Gentry and Lukas, 2002). Exposure of human neuroblastoma SH-SY5Y cells (which express ganglionic alpha7 and alpha3* nAChRs), human TE671/RD cells, or mouse BC3H-1 cells (which express muscle-type nAChRs) to nicotine for up to 120 h induces a dose- and time-dependent increase in surface ACh and alpha-bungarotoxin (alpha-BTX) binding not attributable to changes in mRNA levels (Ke et al., 1998). PubMed:19293145

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Experimental Factor Ontology (EFO)
SH-SY5Y

p(HGNC:ACHE) decreases a(CHEBI:acetylcholine) View Subject | View Object

Several lines of evidence point to a link between brain nAChRs and the development of AD. Biochemical analysis of brains of patients with AD reveals deficits in nAChRs, an increase in butyrylcholinesterase, reduction in ACh, and attenuated activity of cholinergic synthetic [choline acetyltransferase (ChAT)] and inactivating (AChE) enzymes (Bartus et al., 1982; Francis et al., 1999).Butyrylcholinesterase and AChE help terminate ACh signaling by hydrolyzing the transmitter, thereby inactivating it. PubMed:19293145

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p(HGNC:BCHE) decreases a(CHEBI:acetylcholine) View Subject | View Object

Several lines of evidence point to a link between brain nAChRs and the development of AD. Biochemical analysis of brains of patients with AD reveals deficits in nAChRs, an increase in butyrylcholinesterase, reduction in ACh, and attenuated activity of cholinergic synthetic [choline acetyltransferase (ChAT)] and inactivating (AChE) enzymes (Bartus et al., 1982; Francis et al., 1999).Butyrylcholinesterase and AChE help terminate ACh signaling by hydrolyzing the transmitter, thereby inactivating it. PubMed:19293145

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p(HGNC:CHRNA7, pmod(Ph)) decreases act(a(CHEBI:acetylcholine)) View Subject | View Object

Genistein enhances the amplitude of ACh responses when human alpha7 nAChRs are expressed in Xe- nopus laevis oocytes by inhibiting phosphorylation of the receptor in the intracellular loop (Charpantier et al., 2005; Grønlien et al., 2007) and shows similar actions on alpha7 nAChRs of rat hippocampal and supraoptic nucleus neurons as well as human SH-SY5Y cells (Charpantier et al., 2005). PubMed:19293145

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path(MESH:"Alzheimer Disease") decreases a(CHEBI:acetylcholine) View Subject | View Object

Several lines of evidence point to a link between brain nAChRs and the development of AD. Biochemical analysis of brains of patients with AD reveals deficits in nAChRs, an increase in butyrylcholinesterase, reduction in ACh, and attenuated activity of cholinergic synthetic [choline acetyltransferase (ChAT)] and inactivating (AChE) enzymes (Bartus et al., 1982; Francis et al., 1999).Butyrylcholinesterase and AChE help terminate ACh signaling by hydrolyzing the transmitter, thereby inactivating it. PubMed:19293145

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a(HBP:VU10010) increases act(a(CHEBI:acetylcholine)) View Subject | View Object

Two novel M4-selective compounds, VU10010 and LY2033298, represented a breakthrough when they were described in 2008.84,85 VU10010 is a potent M4-selective PAM that increases affinity/efficacy of ACh to promote M4 mAChR activation. PubMed:24511233

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act(p(HGNC:CHRM1)) increases a(CHEBI:acetylcholine) View Subject | View Object

The first subtype-selective M1 PAM to be characterized was benzyl quinolone carboxylic acid (BQCA);68 BQCA exhibited high selectivity with no activity at mAChR subtypes M2–M5 and induced up to a 129-fold leftward shift in ACh potency at the M1 mAChR PubMed:24511233

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p(HGNCGENEFAMILY:"Cholinergic receptors muscarinic") regulates act(a(CHEBI:acetylcholine)) View Subject | View Object

Acetylcholine (ACh) is a neurotransmitter that modulates neuronal function in several areas of the CNS associated with AD and/or SZ pathology, including the striatum, cortex, hippocampus, and prefrontal cortex.5 ACh mediates its actions via two families of receptors, termed the muscarinic ACh receptors (mAChRs) and the nicotinic ACh receptors (nAChRs). PubMed:24511233

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MeSH
Cerebral Cortex
MeSH
Corpus Striatum
MeSH
Hippocampus
MeSH
Prefrontal Cortex

p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") regulates act(a(CHEBI:acetylcholine)) View Subject | View Object

Acetylcholine (ACh) is a neurotransmitter that modulates neuronal function in several areas of the CNS associated with AD and/or SZ pathology, including the striatum, cortex, hippocampus, and prefrontal cortex.5 ACh mediates its actions via two families of receptors, termed the muscarinic ACh receptors (mAChRs) and the nicotinic ACh receptors (nAChRs). PubMed:24511233

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MeSH
Cerebral Cortex
MeSH
Corpus Striatum
MeSH
Hippocampus
MeSH
Prefrontal Cortex

a(CHEBI:"amyloid-beta") decreases a(CHEBI:acetylcholine) View Subject | View Object

Although Aβ peptides negatively alter the cholinergic system at multiple sites, including ACh synthesis, ACh release, and muscarinic receptors (157), the discovery that Aβ1−42 binds to α7 nAChRs with high affinity suggested the potential for a causal role of nAChRs in AD (159, 160). PubMed:17009926

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MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta") decreases sec(a(CHEBI:acetylcholine)) View Subject | View Object

Although Aβ peptides negatively alter the cholinergic system at multiple sites, including ACh synthesis, ACh release, and muscarinic receptors (157), the discovery that Aβ1−42 binds to α7 nAChRs with high affinity suggested the potential for a causal role of nAChRs in AD (159, 160). PubMed:17009926

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MeSH
Alzheimer Disease

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases sec(a(CHEBI:acetylcholine)) View Subject | View Object

Exogenously applied nicotinic agonists enhance and nicotinic antagonists often diminish the release of ACh, dopamine (DA), norepinephrine, and serotonin, as well as glutamate and GABA. PubMed:17009926

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a(CHEBI:"nicotinic antagonist") decreases sec(a(CHEBI:acetylcholine)) View Subject | View Object

Exogenously applied nicotinic agonists enhance and nicotinic antagonists often diminish the release of ACh, dopamine (DA), norepinephrine, and serotonin, as well as glutamate and GABA. PubMed:17009926

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deg(a(CHEBI:acetylcholine)) decreases act(a(CHEBI:acetylcholine)) View Subject | View Object

Unlike many neurotransmitter signals that are shaped by pumps that return the transmitter to the intracellular space, the spread of ACh from the release site is determined by diffusion and by acetylcholinesterase (AChE) hydrolysis of ACh. PubMed:17009926

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bp(GO:"synaptic transmission, cholinergic") increases act(a(CHEBI:acetylcholine)) View Subject | View Object

Cholinergic volume transmission enables ACh to diffuse and to act at lower concentrations some distance away from the release site. PubMed:17009926

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composite(a(CHEBI:"5-hydroxyindole"), a(CHEBI:acetylcholine)) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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composite(a(CHEBI:acetylcholine), a(CHEBI:ivermectin)) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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act(p(HGNC:ACHE), ma(pep)) directlyIncreases deg(a(CHEBI:acetylcholine)) View Subject | View Object

Unlike many neurotransmitter signals that are shaped by pumps that return the transmitter to the intracellular space, the spread of ACh from the release site is determined by diffusion and by acetylcholinesterase (AChE) hydrolysis of ACh. PubMed:17009926

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rxn(reactants(a(CHEBI:acetylcholine)), products(a(CHEBI:acetate), a(CHEBI:choline))) hasReactant a(CHEBI:acetylcholine) View Subject | View Object

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a(CHEBI:"2-(4-phenyl-1-piperidinyl)-1-cyclohexanol") decreases tloc(a(CHEBI:acetylcholine), fromLoc(GO:cytosol), toLoc(MESH:"Synaptic Vesicles")) View Subject | View Object

The vesicular transporter activity can be blocked by vesamicol, which is a non-competitive inhibitor PubMed:26813123

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a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

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MeSH
Synapses

a(CHEBI:choline) increases a(CHEBI:acetylcholine) View Subject | View Object

CHT1 is mainly found in cholinergic neurons [92-94] and is responsible for supplying choline for the synthesis of ACh PubMed:26813123

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Cell Ontology (CL)
cholinergic neuron

a(MESH:"Cholinergic Neurons") increases a(CHEBI:acetylcholine) View Subject | View Object

ACh synthesis takes place in the cytoplasm of cholinergic neurons PubMed:26813123

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MeSH
Cytoplasm

a(MESH:"Cholinesterase Inhibitors") increases a(CHEBI:acetylcholine) View Subject | View Object

Cholinesterase inhibitors can increase ACh levels in the synaptic cleft and partially ameliorate cognitive symptoms, enhance quality of life and diminish caregiver burden for patients with mild to severe AD PubMed:26813123

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MeSH
Alzheimer Disease

a(PUBCHEM:9867750) increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Moreover, the use of M2 antagonists, such as SCH-57790 and SC-72788, can lead to blockage of M2-mediated inhibition of presynaptic release of ACh, which can activate M1 and nicotinic receptors, ameliorating cognitive impairment in AD PubMed:26813123

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MeSH
Alzheimer Disease

bp(GO:"action potential initiation") increases a(CHEBI:acetylcholine) View Subject | View Object

Interestingly, it has been demonstrated that an increase in neuronal firing can lead to an increase in choline uptake and in the synthesis of ACh PubMed:26813123

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bp(GO:"action potential initiation") increases a(CHEBI:acetylcholine) View Subject | View Object

It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis PubMed:26813123

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MeSH
Membranes
MeSH
Synaptic Vesicles

bp(GO:"membrane depolarization") increases tloc(a(CHEBI:acetylcholine), fromLoc(MESH:"Synaptic Vesicles"), toLoc(GO:"synaptic cleft")) View Subject | View Object

When cholinergic neurons are depolarized, ACh is exocytosed from synaptic vesicles and released into the synaptic cleft, where it can activate both muscarinic and nicotinic receptors PubMed:26813123

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Cell Ontology (CL)
cholinergic neuron

bp(GO:"response to stress") regulates tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(MESH:"Basal Forebrain")) View Subject | View Object

Stress is another factor that can regulate ACh release in the forebrain and its function on the hypothalamic-pituitaryadrenal (HPA) system can modulate biological and emotional outcomes PubMed:26813123

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bp(GO:cognition) association a(CHEBI:acetylcholine) View Subject | View Object

Because ACh has an important role in cognitive processes, the cholinergic system is pointed as an important factor in many forms of dementia, including AD PubMed:26813123

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bp(GO:learning) association a(CHEBI:acetylcholine) View Subject | View Object

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

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bp(GO:memory) positiveCorrelation a(CHEBI:acetylcholine) View Subject | View Object

Moreover, published data indicate that ACh is involved in memory PubMed:26813123

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bp(GO:memory) association a(CHEBI:acetylcholine) View Subject | View Object

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

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p(HGNC:SLC5A7) increases a(CHEBI:acetylcholine) View Subject | View Object

It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis PubMed:26813123

Appears in Networks:
Annotations
MeSH
Membranes
MeSH
Synaptic Vesicles

p(HGNC:ACHE) decreases act(a(CHEBI:acetylcholine)) View Subject | View Object

ACh present at the synaptic cleft is rapidly inactivated by the enzyme acetylcholinesterase (AChE), releasing choline and acetate PubMed:26813123

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p(HGNC:CHRM2) decreases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Moreover, the use of M2 antagonists, such as SCH-57790 and SC-72788, can lead to blockage of M2-mediated inhibition of presynaptic release of ACh, which can activate M1 and nicotinic receptors, ameliorating cognitive impairment in AD PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:SLC18A3) increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:cytosol), toLoc(MESH:"Synaptic Vesicles")) View Subject | View Object

Following that, the neurotransmitter is transported by the vesicular acetylcholine transporter (VAChT) from the cytosol into synaptic vesicles PubMed:26813123

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p(HGNC:SLC18A3) increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:cytosol), toLoc(MESH:"Synaptic Vesicles")) View Subject | View Object

Each molecule of ACh transported by VAChT is in exchange for two vesicular protons, which leads to the fulfill of synaptic vesicles with the neurotransmitter PubMed:26813123

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a(MESH:D002800) increases a(CHEBI:acetylcholine) View Subject | View Object

Pyramidal neurons, which account for ~70% of all neurons in the neocortex, use glutamate as their primary neurotransmitter. Nonetheless, in addition to possessing glutamatergic receptors on their surface, these neurons often also possess cholinergic receptors, which are capable of receiving cholinergic inputs into the neocortex from the basal forebrain. The presence of these cholinergic receptors has been putatively linked to an important finding regarding the interaction between the cholinergic and glutamatergic neurotransmission systems. In particular, rodent studies have revealed that cholinesterase inhibitors (ChEIs) promote the release of glutamate from pyramidal neurons,16 with the proposed explanation being that ChEI administration leads to increased cortical ACh concentrations and, consequently, increased binding of ACh by cholinergic receptors on pyramidal neurons, thereby stimulating neuronal firing (ie, glutamate release). PubMed:16273023

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Cell Ontology (CL)
pyramidal neuron
MeSH
Neocortex

complex(a(CHEBI:acetylcholine), p(MESH:D011950)) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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complex(a(CHEBI:acetylcholine), p(MESH:D011950)) increases a(CHEBI:acetylcholine) View Subject | View Object

Pyramidal neurons, which account for ~70% of all neurons in the neocortex, use glutamate as their primary neurotransmitter. Nonetheless, in addition to possessing glutamatergic receptors on their surface, these neurons often also possess cholinergic receptors, which are capable of receiving cholinergic inputs into the neocortex from the basal forebrain. The presence of these cholinergic receptors has been putatively linked to an important finding regarding the interaction between the cholinergic and glutamatergic neurotransmission systems. In particular, rodent studies have revealed that cholinesterase inhibitors (ChEIs) promote the release of glutamate from pyramidal neurons,16 with the proposed explanation being that ChEI administration leads to increased cortical ACh concentrations and, consequently, increased binding of ACh by cholinergic receptors on pyramidal neurons, thereby stimulating neuronal firing (ie, glutamate release). PubMed:16273023

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Annotations
Cell Ontology (CL)
pyramidal neuron
MeSH
Neocortex

act(p(HGNC:CHAT), ma(cat)) increases a(CHEBI:acetylcholine) View Subject | View Object

For example, the activity of choline acetyltransferase, the enzyme that catalyzes the synthesis of ACh from choline and acetyl coenzyme A, is reduced to 35% to 50% of normal levels in Alzheimer's disease PubMed:16273023

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complex(a(CHEBI:acetylcholine), p(FPLX:"G_protein"), p(HGNCGENEFAMILY:"Cholinergic receptors muscarinic")) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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complex(a(CHEBI:acetylcholine), p(HGNC:CHRM1)) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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p(HGNC:CHAT) decreases a(CHEBI:acetylcholine) View Subject | View Object

The third important hallmark of AD is cholinergic hypofunction. The neurotransmitter acetylcholine (ACh) exerts its physiological functions by activating either ionotropic nicotinic ACh receptors (nAChRs) or metabotropic muscarinic ACh receptors (mAChRs). It has been reported that in AD brains there are (1) reduced choline acetyltransferase levels accompanied by decreased ACh synthesis; (2) significant loss of cholinergic neurons; (3) reduction in the numbers of postsynaptic neurons accessible to ACh; (4) cholinergic neuronal and axonal abnormalities; and (5) reduction in nAChR levels PubMed:24590577

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a(CHEBI:"amyloid-beta") increases act(a(CHEBI:acetylcholine)) View Subject | View Object

A different set of experiments demonstrated that Abeta enhances ACh activation of the alpha4beta2 nAChRs expressed in oocytes, this first activation of the receptor was followed by its inhibition (Pym et al., 2005) PubMed:25514383

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Cell Ontology (CL)
oocyte

complex(a(CHEBI:acetylcholine), p(FPLX:CHRN)) hasComponent a(CHEBI:acetylcholine) View Subject | View Object

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act(p(HGNC:CHAT)) increases a(CHEBI:acetylcholine) View Subject | View Object

In addition to nAChRs and mAChRs, the enzyme choline acetyltransferase (ChAT), involved in ACh production, is also affected in AD. The activity of this ChAT enzyme, and consequently the synthesis of ACh, is decreased in AD brains PubMed:25514383

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MeSH
Brain

path(MESH:"Alzheimer Disease") decreases a(CHEBI:acetylcholine) View Subject | View Object

In addition to nAChRs and mAChRs, the enzyme choline acetyltransferase (ChAT), involved in ACh production, is also affected in AD. The activity of this ChAT enzyme, and consequently the synthesis of ACh, is decreased in AD brains PubMed:25514383

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MeSH
Brain

a(MESH:"Presynaptic Terminals") increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

The ‘‘volume transmission’’ hypothesis states that ACh released from presynaptic terminals spreads to more distant areas, reaching concentrations < 1 mM (Descarries et al., 1997), but that multiple presynaptic impulses produce enough summed release to activate receptors (Lester, 2004) PubMed:21482353

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p(HGNC:ACHE) increases deg(a(CHEBI:acetylcholine)) View Subject | View Object

In most regions that receive cholinergic innervation, the high density of acetylcholinesterase (which can hydrolyze ACh at a rate of one per 100 ms!) might vitiate the volume transmission mechanism PubMed:21482353

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act(p(HGNC:BCHE), ma(cat)) directlyIncreases deg(a(CHEBI:acetylcholine)) View Subject | View Object

Butyrylcholinesterase (BChE) is a serine hydrolase similar to AChE that is widely distributed throughout the CNS and also catalyzes the hydrolysis of ACh. BChE is localized to neurons and glia, and is associated with NFTs and senile plaques (SPs) in AD brain [32]. Interestingly, population-based genetic studies of AD have identified a point mutation that changes Ala539 to threonine in the K variant of BChE, which effectively reduces serum BChE concentrations, and may be associated with cognitive decline [33]. BChE activity also increases in AD brain whereas AChE activity remains unchanged or declines [34,35]. PubMed:18986241

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Disease Ontology (DO)
Alzheimer's disease
MeSH
Neuroglia
MeSH
Neurons
MeSH
Cognitive Dysfunction

act(p(HGNC:CHAT)) directlyIncreases a(CHEBI:acetylcholine) View Subject | View Object

Notably, reports that physostigmine and oral anticholinesterases have beneficial effects for patients with AD suggest that the CBF system is somewhat preserved during the progression of dementia, despite well-documented loss of cholinergic biosynthetic machinery (including ChAT and AChE enzyme deficits) in patients with this disease. Interestingly, recent studies have shown that ChAT activity, which results in acetylcholine (ACh) synthesis, is preserved in the neocortex of people with MCI [18,19]. PubMed:18986241

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MeSH
Neocortex
MeSH
Cognitive Dysfunction

bp(GO:cognition) negativeCorrelation a(CHEBI:acetylcholine) View Subject | View Object

Cholinergic therapy is based on the assumption that low levels of acetylcholine are responsible for the cognitive decline associated with AD PubMed:11230871

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MeSH
Alzheimer Disease

a(HBP:"B-973") increases act(a(CHEBI:acetylcholine)) View Subject | View Object

Over the concentration range studied, B-973 increased the potency of acetylcholine at the α7 receptor 70-fold (control acetylcholine EC50=0.49 mM; acetylcholine EC50 at 1 μM B-973=0.007 mM) PubMed:28132910

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bp(GO:"regulation of cation channel activity") association a(CHEBI:acetylcholine) View Subject | View Object

The acute effect of ACh consists of the fast opening (microsecond to millisecond range) of a cationic channel that is permeable to Na+, K+ and sometimes Ca2+ ions. PubMed:19721446

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Text Location
Review

p(HGNC:CHAT) increases a(CHEBI:acetylcholine) View Subject | View Object

ACh is produced by the enzyme choline acetyltransferase and its actions are mediated through two types of acetylcholine receptors (AChRs) — the G protein-coupled muscarinic AChRs and the nicotinic AChRs (nAChRs). PubMed:19721446

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Review

p(HGNCGENEFAMILY:"Cholinergic receptors muscarinic") increases act(a(CHEBI:acetylcholine)) View Subject | View Object

ACh is produced by the enzyme choline acetyltransferase and its actions are mediated through two types of acetylcholine receptors (AChRs) — the G protein-coupled muscarinic AChRs and the nicotinic AChRs (nAChRs). PubMed:19721446

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Text Location
Review

p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") increases act(a(CHEBI:acetylcholine)) View Subject | View Object

ACh is produced by the enzyme choline acetyltransferase and its actions are mediated through two types of acetylcholine receptors (AChRs) — the G protein-coupled muscarinic AChRs and the nicotinic AChRs (nAChRs). PubMed:19721446

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Text Location
Review

a(CHEBI:galanthamine) increases a(CHEBI:acetylcholine) View Subject | View Object

It inhibits AChE competitively and reversibly, causing elevated cerebral concen-trations of ACh, and thus, enhancing cholinergic activity. PubMed:29179999

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MeSH
Cerebral Cortex

a(CHEBI:galanthamine) increases sec(a(CHEBI:acetylcholine)) View Subject | View Object

Besides, galantamine allosterically interacted with nicotinic ACh receptors to increase the agonistic activity of these receptors and amplified the ACh reaction through stimulating ACh release [165–167]. PubMed:29179999

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Out-Edges 36

a(CHEBI:acetylcholine) increases act(p(HGNCGENEFAMILY:"Cholinergic receptors muscarinic")) View Subject | View Object

Acetylcholine receptors (AChRs), like many other ligand-activated neurotransmitter receptors, consist of two major subtypes: the metabotropic muscarinic receptors and the ionotropic nicotinic receptors. Both share the property of being activated by the endogenous neurotransmitter acetylcholine (ACh), and they are expressed by both neuronal and nonneuronal cells throughout the body (8, 113, 142, 184). PubMed:19126755

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Text Location
Review

a(CHEBI:acetylcholine) increases act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

Acetylcholine receptors (AChRs), like many other ligand-activated neurotransmitter receptors, consist of two major subtypes: the metabotropic muscarinic receptors and the ionotropic nicotinic receptors. Both share the property of being activated by the endogenous neurotransmitter acetylcholine (ACh), and they are expressed by both neuronal and nonneuronal cells throughout the body (8, 113, 142, 184). PubMed:19126755

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Text Location
Review

a(CHEBI:acetylcholine) decreases path(MESH:"Heart Rate") View Subject | View Object

From the time of its discovery in 1914 by Henry H. Dale (109) and Otto Loewi (283) (the two shared the Nobel Prize in Physiology and Medicine in 1936) as an agent that decreases heart rate, ACh was recognized as an endogenous signaling compound, synthesized from choline and acetyl-CoA, through the action of choline acetyltransferase, that alters cell function. PubMed:19126755

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Text Location
Review

a(CHEBI:acetylcholine) association bp(GO:signaling) View Subject | View Object

From the time of its discovery in 1914 by Henry H. Dale (109) and Otto Loewi (283) (the two shared the Nobel Prize in Physiology and Medicine in 1936) as an agent that decreases heart rate, ACh was recognized as an endogenous signaling compound, synthesized from choline and acetyl-CoA, through the action of choline acetyltransferase, that alters cell function. PubMed:19126755

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Annotations
Text Location
Review

a(CHEBI:acetylcholine) increases act(p(FPLX:CHRN)) View Subject | View Object

We now realize that acetylcholine liberated from cholinergic nerve terminals often activates both nAChRs and muscarinic receptors PubMed:21482353

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a(CHEBI:acetylcholine) regulates act(a(MESH:Neurons)) View Subject | View Object

Acetylcholine (ACh) is a neurotransmitter that modulates neuronal function in several areas of the CNS associated with AD and/or SZ pathology, including the striatum, cortex, hippocampus, and prefrontal cortex.5 ACh mediates its actions via two families of receptors, termed the muscarinic ACh receptors (mAChRs) and the nicotinic ACh receptors (nAChRs). PubMed:24511233

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MeSH
Cerebral Cortex
MeSH
Corpus Striatum
MeSH
Hippocampus
MeSH
Prefrontal Cortex

act(a(CHEBI:acetylcholine)) increases act(p(HGNC:CHRM1)) View Subject | View Object

Two novel M4-selective compounds, VU10010 and LY2033298, represented a breakthrough when they were described in 2008.84,85 VU10010 is a potent M4-selective PAM that increases affinity/efficacy of ACh to promote M4 mAChR activation. PubMed:24511233

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deg(a(CHEBI:acetylcholine)) decreases act(a(CHEBI:acetylcholine)) View Subject | View Object

Unlike many neurotransmitter signals that are shaped by pumps that return the transmitter to the intracellular space, the spread of ACh from the release site is determined by diffusion and by acetylcholinesterase (AChE) hydrolysis of ACh. PubMed:17009926

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a(CHEBI:acetylcholine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

The α7 nAChR has a relatively low affinity for ACh activation, with an effective dose for half-activation at approximately 200 μM ACh. PubMed:17009926

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a(CHEBI:acetylcholine) increases bp(GO:"regulation of action potential firing rate") View Subject | View Object

In most cases, the exogenously applied ACh caused action potential firing by the GABA neuron that consequently regulated the activity of nearby pyramidal neurons (100, 103). PubMed:17009926

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MeSH
GABAergic Neurons

a(CHEBI:acetylcholine) positiveCorrelation bp(GO:memory) View Subject | View Object

Moreover, published data indicate that ACh is involved in memory PubMed:26813123

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a(CHEBI:acetylcholine) isA a(CHEBI:neurotransmitter) View Subject | View Object

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a(CHEBI:acetylcholine) regulates bp(GO:memory) View Subject | View Object

Further studies have demonstrated that endogenous acetylcholine is important for modulation of acquisition [17], encoding [18], consolidation [19], reconsolidation [20], extinction [21] and retrieval of memory PubMed:26813123

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a(CHEBI:acetylcholine) association bp(GO:memory) View Subject | View Object

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

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a(CHEBI:acetylcholine) regulates a(MESH:"Hypothalamo-Hypophyseal System") View Subject | View Object

Stress is another factor that can regulate ACh release in the forebrain and its function on the hypothalamic-pituitaryadrenal (HPA) system can modulate biological and emotional outcomes PubMed:26813123

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a(CHEBI:acetylcholine) increases act(a(MESH:"Receptors, Nicotinic")) View Subject | View Object

Similarly, nicotine can mimic the ACh effects on the HPA axis by activating nicotinic receptors PubMed:26813123

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a(CHEBI:acetylcholine) increases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

ACh contributes to auditory synaptic transmission by facilitating thalamocortical communication PubMed:26813123

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a(CHEBI:acetylcholine) increases bp(GO:neurogenesis) View Subject | View Object

Recent evidences also suggest the involvement of ACh in adult neurogenesis PubMed:26813123

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a(CHEBI:acetylcholine) increases act(p(FPLX:CHRM)) View Subject | View Object

When cholinergic neurons are depolarized, ACh is exocytosed from synaptic vesicles and released into the synaptic cleft, where it can activate both muscarinic and nicotinic receptors PubMed:26813123

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a(CHEBI:acetylcholine) increases act(p(FPLX:CHRN)) View Subject | View Object

When cholinergic neurons are depolarized, ACh is exocytosed from synaptic vesicles and released into the synaptic cleft, where it can activate both muscarinic and nicotinic receptors PubMed:26813123

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deg(a(CHEBI:acetylcholine)) increases a(CHEBI:choline) View Subject | View Object

Choline that is released by ACh hydrolysis in the synaptic cleft is continuously reuptaken into the presynaptic cholinergic neuron by an active transport system (see Fig. 1) PubMed:26813123

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a(CHEBI:acetylcholine) regulates bp(MESH:"Synaptic Transmission") View Subject | View Object

Thus, ACh can influence the strength and fidelity of various synapses and modulate overall CNS neurotransmission PubMed:26813123

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MeSH
Central Nervous System

a(CHEBI:acetylcholine) regulates bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

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a(CHEBI:acetylcholine) association bp(GO:learning) View Subject | View Object

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission PubMed:26813123

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a(CHEBI:acetylcholine) association bp(GO:cognition) View Subject | View Object

Because ACh has an important role in cognitive processes, the cholinergic system is pointed as an important factor in many forms of dementia, including AD PubMed:26813123

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a(CHEBI:acetylcholine) increases complex(a(CHEBI:acetylcholine), p(MESH:D011950)) View Subject | View Object

Pyramidal neurons, which account for ~70% of all neurons in the neocortex, use glutamate as their primary neurotransmitter. Nonetheless, in addition to possessing glutamatergic receptors on their surface, these neurons often also possess cholinergic receptors, which are capable of receiving cholinergic inputs into the neocortex from the basal forebrain. The presence of these cholinergic receptors has been putatively linked to an important finding regarding the interaction between the cholinergic and glutamatergic neurotransmission systems. In particular, rodent studies have revealed that cholinesterase inhibitors (ChEIs) promote the release of glutamate from pyramidal neurons,16 with the proposed explanation being that ChEI administration leads to increased cortical ACh concentrations and, consequently, increased binding of ACh by cholinergic receptors on pyramidal neurons, thereby stimulating neuronal firing (ie, glutamate release). PubMed:16273023

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Cell Ontology (CL)
pyramidal neuron
MeSH
Neocortex

a(CHEBI:acetylcholine) increases act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

The third important hallmark of AD is cholinergic hypofunction. The neurotransmitter acetylcholine (ACh) exerts its physiological functions by activating either ionotropic nicotinic ACh receptors (nAChRs) or metabotropic muscarinic ACh receptors (mAChRs). It has been reported that in AD brains there are (1) reduced choline acetyltransferase levels accompanied by decreased ACh synthesis; (2) significant loss of cholinergic neurons; (3) reduction in the numbers of postsynaptic neurons accessible to ACh; (4) cholinergic neuronal and axonal abnormalities; and (5) reduction in nAChR levels PubMed:24590577

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a(CHEBI:acetylcholine) increases act(p(HGNCGENEFAMILY:"Cholinergic receptors muscarinic")) View Subject | View Object

The third important hallmark of AD is cholinergic hypofunction. The neurotransmitter acetylcholine (ACh) exerts its physiological functions by activating either ionotropic nicotinic ACh receptors (nAChRs) or metabotropic muscarinic ACh receptors (mAChRs). It has been reported that in AD brains there are (1) reduced choline acetyltransferase levels accompanied by decreased ACh synthesis; (2) significant loss of cholinergic neurons; (3) reduction in the numbers of postsynaptic neurons accessible to ACh; (4) cholinergic neuronal and axonal abnormalities; and (5) reduction in nAChR levels PubMed:24590577

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tloc(a(CHEBI:acetylcholine), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) regulates bp(GO:"long-term memory") View Subject | View Object

Woolf (1998) proposed a model in which acetylcholine (ACh) release leads to the modulation of cortical circuitry that finally encodes for storage of long-term memory PubMed:25514383

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a(CHEBI:acetylcholine) increases act(a(HBP:"beta-2-containing nAChR")) View Subject | View Object

Aged beta2 null mutant mice have a thinner cortex compared to agematched wild-type controls (Zoli et al., 1999). This work should be pursued further as it indicates a “neurotrophic” action of beta2 receptor activation by endogenous ACh (Zanardi et al., 2007) PubMed:25514383

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act(a(CHEBI:acetylcholine)) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

A different set of experiments demonstrated that Abeta enhances ACh activation of the alpha4beta2 nAChRs expressed in oocytes, this first activation of the receptor was followed by its inhibition (Pym et al., 2005) PubMed:25514383

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Cell Ontology (CL)
oocyte

a(CHEBI:acetylcholine) increases act(p(FPLX:CHRM)) View Subject | View Object

We now realize that acetylcholine liberated from cholinergic nerve terminals often activates both nAChRs and muscarinic receptors PubMed:21482353

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a(CHEBI:acetylcholine) increases act(a(HBP:"alpha-7-containing nAChR")) View Subject | View Object

A possible candidate is choline, which, in addition to its other development roles, activates alpha7 nAChRs at levels several fold higher than acetylcholine PubMed:21482353

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a(CHEBI:acetylcholine) negativeCorrelation bp(GO:cognition) View Subject | View Object

Cholinergic therapy is based on the assumption that low levels of acetylcholine are responsible for the cognitive decline associated with AD PubMed:11230871

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MeSH
Alzheimer Disease

a(CHEBI:acetylcholine) association bp(GO:"regulation of cation channel activity") View Subject | View Object

The acute effect of ACh consists of the fast opening (microsecond to millisecond range) of a cationic channel that is permeable to Na+, K+ and sometimes Ca2+ ions. PubMed:19721446

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Text Location
Review

a(CHEBI:acetylcholine) increases act(p(FPLX:CHRN)) View Subject | View Object

In terms of functional effects, nicotine acts acutely much in the way that ACh does, causing opening of nAChR channels. PubMed:21787755

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About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.