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PubMed: 17009926

Title
Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.
Journal
Annual review of pharmacology and toxicology
Volume
47
Issue
None
Pages
699-729
Date
2007-01-01
Authors
Bertrand D | Dani JA

Evidence 9b88b3a7c6
JSON

Ivermectin is an example of a positive allosteric effector that modifies the pharmacological profile of the α7 nAChR.

a(CHEBI:ivermectin) regulates act(p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:

Evidence 245fc4302c
JSON

Activation and desensitization of nAChRs by bath-applied nicotine also increases LTD induced by a stimulus train

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

Appears in Networks:

act(p(FPLX:CHRN)) increases bp(GO:"long term synaptic depression") View Subject | View Object

Appears in Networks:

Evidence b7bb57d804
JSON

The nicotine initially activates nAChRs on DA neurons, causing an increase in burst firing and overall firing rate (88, 121, 123, 124, 134).

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

Appears in Networks:
Annotations
Cell Ontology (CL)
dopaminergic neuron

p(FPLX:CHRN) increases bp(GO:"regulation of action potential firing rate") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
dopaminergic neuron

Evidence 8ea0831b0c
JSON

Results show that genistein does not alter the surface expression of nAChRs, but rather it modifies nAChRs in the cell membrane (71).

a(CHEBI:genistein) regulates p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cell Membrane

a(CHEBI:genistein) causesNoChange surf(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence 502566d5f7
JSON

Another allosteric effector, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), dramatically modifies the response time course, ampliude of the current, and agonist sensitivity of the rat and human α7 nAChRs (70).

a(CHEBI:"1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methyl-3-isoxazolyl)urea") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:

Evidence 5c46381633
JSON

The most commonly prescribed treatments for AD are acetylcholinesterase inhibitors, which decrease the hydrolysis rate of ACh and, thereby, enhance cholinergic signaling. One such drug, galantamine (Reminyl), also potentiates nAChRs (66).

a(CHEBI:"EC 3.1.1.7 (acetylcholinesterase) inhibitor") decreases path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"EC 3.1.1.7 (acetylcholinesterase) inhibitor") decreases act(p(HGNC:ACHE)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"EC 3.1.1.7 (acetylcholinesterase) inhibitor") decreases rxn(reactants(a(CHEBI:acetylcholine)), products(a(CHEBI:acetate), a(CHEBI:choline))) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"EC 3.1.1.7 (acetylcholinesterase) inhibitor") increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 3b30b53f16
JSON

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).

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

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta") decreases act(p(FPLX:CHRM)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(a(CHEBI:"amyloid-beta polypeptide 42"), p(HGNC:CHRNA7)) association path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") association complex(a(CHEBI:"amyloid-beta polypeptide 42"), p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence fe04459aac
JSON

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161).

a(CHEBI:"amyloid-beta") positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta") positiveCorrelation p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

a(HBP:"amyloid-beta aggregates") association p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) association a(HBP:"amyloid-beta aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA4) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA4) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 35d8324899
JSON

This calcium influx can trigger calcium-induced calcium release from intracellular stores (86).

tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(GO:cytosol)) View Subject | View Object

Appears in Networks:

Evidence 5c6853e618
JSON

For example, local infusion of the α7 antagonist, methyllycaconitine (MLA), or the β2∗ antagonist, dihydro-β-erythroidine (DHβE), into the basolateral amygdala, the ventral hippocampus, or the dorsal hippocampus impairs the working memory of rats seeking food reward within a 16-arm radial maze (146–148).

a(CHEBI:"dihydro-beta-erythroidine") decreases act(p(HGNC:CHRNB2)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala
MeSH
Hippocampus

a(CHEBI:"dihydro-beta-erythroidine") decreases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala
MeSH
Hippocampus

a(PUBCHEM:5311278) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala
MeSH
Hippocampus

a(PUBCHEM:5311278) decreases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Amygdala
MeSH
Hippocampus

Evidence 4d4e70c900
JSON

The combination of enhanced glutamatergic release and strong postsynaptic response produces LTP of the glutamatergic afferents.

sec(a(CHEBI:"glutamate(2-)")) increases bp(GO:"long-term synaptic potentiation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glutamatergic neuron

bp(GO:"depolarization of postsynaptic membrane") increases bp(GO:"long-term synaptic potentiation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glutamatergic neuron

Evidence ed8efa06c7
JSON

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.

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases sec(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

a(CHEBI:"nicotinic antagonist") decreases sec(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Appears in Networks:

a(CHEBI:"nicotinic antagonist") decreases sec(a(CHEBI:"gamma-aminobutyric acid")) View Subject | View Object

Appears in Networks:

Evidence 8a002ab12a
JSON

In general, nicotinic agonists improve certain forms of memory, and nicotinic antagonists and cholinergic lesions impair memory (5, 141–145).

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases bp(GO:memory) View Subject | View Object

Appears in Networks:

a(CHEBI:"nicotinic antagonist") decreases bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence 51e6bf3da9
JSON

In animal studies, acute and chronic nicotine administration improves working memory, and nicotinic agonists were found to improve learning and memory in humans and nonhuman primates (145).

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases bp(GO:memory) View Subject | View Object

Appears in Networks:

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases bp(GO:learning) View Subject | View Object

Appears in Networks:

a(CHEBI:nicotine) increases bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence 8779c6a4fb
JSON

During attention tasks, the nicotinic antagonist, mecamylamine, impaired accuracy or reaction time (151, 152) and nicotinic agonists improved accuracy (153).

a(CHEBI:Mecamylamine) decreases path(MESH:Attention) View Subject | View Object

Appears in Networks:

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases path(MESH:Attention) View Subject | View Object

Appears in Networks:

Evidence 290707e19c
JSON

Consistent with these treatments, nicotinic agents improve cognitive deficits of AD patients (20, 158).

a(CHEBI:"nicotinic acetylcholine receptor agonist") increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 421ffd078a
JSON

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.

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

Appears in Networks:

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

Appears in Networks:

Evidence 77aeb86dd8
JSON

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

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

Appears in Networks:

Evidence 354d7c1728
JSON

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).

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

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

Evidence 6b36d04cfb
JSON

Another important aspect of this diffusive ACh signal is that its eventual hydrolysis creates choline, which also activates and desensitizes nAChRs in a subtype-selective manner (54, 55).

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

Appears in Networks:

act(p(HGNC:ACHE), ma(pep)) directlyIncreases rxn(reactants(a(CHEBI:acetylcholine)), products(a(CHEBI:acetate), a(CHEBI:choline))) View Subject | View Object

Appears in Networks:

Evidence 806838959b
JSON

Dephosphorylation of the α7 receptor by genistein causes a significant increase of ACh-evoked responses without modifying the response time course or ACh sensitivity (71, 72).

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

Appears in Networks:

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

Appears in Networks:

Evidence 1253e236c2
JSON

Nicotine decreases tonic DA release in the striatum that is evoked by single action potentials (127), and nicotine also alters the frequency dependence of DA release that is electrically evoked by stimulus trains (130, 131).

a(CHEBI:nicotine) decreases sec(a(CHEBI:dopamine)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Corpus Striatum

bp(GO:"action potential") increases sec(a(CHEBI:dopamine)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Corpus Striatum

Evidence b370d97b5f
JSON

Simultaneously, nicotine activates presynaptic α7∗ nAChRs, boosting glutamatergic synaptic transmission onto DA neurons (23, 88, 123, 134).

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

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

act(p(HGNC:CHRNA7)) increases bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
dopaminergic neuron

Evidence 7dc3c760e8
JSON

Moreover, although nicotine increases wakefulness in wild-type mice, it does not affect β2−/− mice. Overall, stimulation of nAChRs promotes arousal and REM sleep.

a(CHEBI:nicotine) increases bp(GO:"circadian sleep/wake cycle, wakefulness") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

act(p(FPLX:CHRN)) increases path(MESH:Arousal) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

act(p(FPLX:CHRN)) increases bp(GO:"circadian sleep/wake cycle, REM sleep") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

Evidence a1ae332902
JSON

This effect of preterminal nAChRs is inhibited by tetrodotoxin, which blocks sodium channels and, thus, prevents the regenerative voltage-dependent activation of calcium channels in the presynaptic bouton.

a(CHEBI:tetrodotoxin) decreases act(complex(GO:"voltage-gated calcium channel complex")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

Evidence 571197f169
JSON

Postsynaptic β2∗ nAChRs initially depolarize DA neurons, causing them to fire action potentials while presynaptic α7∗ nAChRs boost glutamate release.

bp(GO:"depolarization of postsynaptic membrane") increases bp(GO:"regulation of action potential firing rate") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
dopaminergic neuron
MeSH
Post-Synaptic Density

act(p(HGNC:CHRNA7)) increases sec(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
dopaminergic neuron
MeSH
Presynaptic Terminals

act(p(HGNC:CHRNB2)) increases bp(GO:"depolarization of postsynaptic membrane") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
dopaminergic neuron
MeSH
Post-Synaptic Density

Evidence 3dcb010d03
JSON

By modulating activity-dependent events, nAChRs participate in fundamental aspects of synaptic plasticity that are involved in attention, learning, memory, and development (3, 12–16).

bp(GO:"developmental process") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

bp(GO:"regulation of synaptic plasticity") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

bp(GO:learning) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

bp(GO:memory) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association bp(GO:"regulation of synaptic plasticity") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:Attention) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association bp(GO:learning) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association bp(GO:memory) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association bp(GO:"developmental process") View Subject | View Object

Appears in Networks:

path(MESH:Attention) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

Evidence 96a8ed2807
JSON

In addition, nAChR activity produces a depolarization that activates voltage-gated calcium channels in the presynaptic terminal (87).

bp(GO:"membrane depolarization") increases act(complex(GO:"voltage-gated calcium channel complex")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

act(p(FPLX:CHRN)) increases bp(GO:"membrane depolarization") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

Evidence 8e0c5a2f31
JSON

The most well-appreciated neuronal loss, however, is in the cholinergic system (155, 156), particularly the basal forebrain cholinergic system comprised of the medial septal nucleus, the horizontal and vertical diagonal bands of Broca, and the nucleus basalis of Meynert (157).

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Alzheimer Disease

Evidence 5ab80f8551
JSON

As AD worsens, cholinergic neurons are progressively lost and the number of nAChRs declines, particularly in the hippocampus and cortex (140, 158).

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

p(FPLX:CHRN) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") negativeCorrelation p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence 89edf2b4e1
JSON

Acting through these excitatory and inhibitory inputs and nAChRs located on the DA neurons, nicotinic receptors influence the firing modes and firing frequency of DA neurons (119, 121).

bp(GO:"regulation of action potential firing pattern") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
midbrain dopaminergic neuron
MeSH
Dendrites
MeSH
Neocortex

bp(GO:"regulation of action potential firing rate") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
midbrain dopaminergic neuron
MeSH
Dendrites
MeSH
Neocortex

p(FPLX:CHRN) association bp(GO:"regulation of action potential firing rate") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
midbrain dopaminergic neuron
MeSH
Dendrites
MeSH
Neocortex

p(FPLX:CHRN) association bp(GO:"regulation of action potential firing pattern") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
midbrain dopaminergic neuron
MeSH
Dendrites
MeSH
Neocortex

Evidence a39a9ad5a0
JSON

Nicotinic receptors also modulate glutamatergic synaptic plasticity.

bp(GO:"regulation of synaptic plasticity") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glutamatergic neuron

p(FPLX:CHRN) association bp(GO:"regulation of synaptic plasticity") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glutamatergic neuron

Evidence c354f6ff62
JSON

Genetic evidence has linked nicotinic receptors to epilepsy and schizophrenia, and studies with mutant mice have implicated nAChRs in pain mechanisms, anxiety, and depression.

p(FPLX:CHRN) association path(MESH:Epilepsy) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:Anxiety) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:Depression) View Subject | View Object

Appears in Networks:

bp(GO:"response to pain") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:Epilepsy) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association bp(GO:"response to pain") View Subject | View Object

Appears in Networks:

path(MESH:Anxiety) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:Depression) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:Schizophrenia) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

Evidence 2a33bff11f
JSON

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

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

Appears in Networks:

Evidence c725e6f435
JSON

In the rat CA3 region, spontaneous activation of GABA A receptors produces giant depolarizing potentials, whose frequency is controlled by α7∗ and non-α7 nAChRs.

act(complex(GO:"GABA-A receptor complex")) increases bp(GO:"membrane depolarization") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

p(FPLX:CHRN) regulates act(complex(GO:"GABA-A receptor complex")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

Evidence c0e4ae62e8
JSON

In some cases, the highly calcium-permeable α7-containing (α7∗) nAChRs mediate the increased release of neurotransmitter, but in other cases different nAChR subtypes are involved.

p(HGNC:CHRNA7) increases bp(GO:"neurotransmitter secretion") View Subject | View Object

Appears in Networks:

Evidence 25976d6703
JSON

Preterminal nAChRs located before the presynaptic terminal bouton indirectly affect neurotransmitter release by activating voltage-gated channels and, potentially, initiating action potentials (78, 91, 93).

p(HGNC:CHRNA7) increases act(complex(GO:"voltage-gated calcium channel complex")) View Subject | View Object

Appears in Networks:

Evidence 313d8fff7f
JSON

Dimethylphenylpiperazidium (DMPP) normally is a partial agonist at this receptor subtype, but it becomes almost a full agonist following ivermectin exposure (68).

composite(a(CHEBI:"1,1-dimethyl-4-phenylpiperazinium iodide"), a(CHEBI:ivermectin)) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:

Evidence 5b901eaa6d
JSON

5-Hydroxy-indol (5-HI) allosterically increases the α7 ACh-induced responses without modifying the response time course or sensitivity to the agonist (69).

composite(a(CHEBI:"5-hydroxyindole"), a(CHEBI:acetylcholine)) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Appears in Networks:

Evidence 17545c437d
JSON

For example, ivermectin increases the apparent ACh affinity, the slope of the dose-response curve, and the amplitude of nAChR responses (68).

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

Appears in Networks:

Evidence e56429c50d
JSON

Subsequent to the original discovery, several other families suffering from typical ADNFLE or nocturnal frontal lobe epilepsy (NFLE) have been found to have a mutation either in α4 or β2 (encoded by CHRNB2) (165, 166, 168–170).

g(HGNC:CHRNA4, var("?")) positiveCorrelation path(MESH:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

g(HGNC:CHRNB2, var("?")) positiveCorrelation path(MESH:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

path(MESH:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") positiveCorrelation g(HGNC:CHRNA4, var("?")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

path(MESH:"Autosomal Dominant Nocturnal Frontal Lobe Epilepsy") positiveCorrelation g(HGNC:CHRNB2, var("?")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

Evidence 9a53b21f65
JSON

Presynaptic and preterminal nicotinic receptors enhance neurotransmitter release, and postsynaptic and nonsynaptic nAChRs mediate excitation as well as activity-dependent modulation of circuits and intracellular enzymatic processes.

p(FPLX:CHRN) increases bp(GO:"neurotransmitter secretion") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

p(FPLX:CHRN) regulates bp(GO:"rhythmic excitation") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) regulates bp(GO:"neuron remodeling") View Subject | View Object

Appears in Networks:

Evidence ac456b77fe
JSON

Activation of presynaptic nAChRs increases the release of many different neurotransmitters (1, 2, 4, 5, 40, 41, 77–83).

act(p(FPLX:CHRN)) increases bp(GO:"neurotransmitter secretion") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Presynaptic Terminals

Evidence 0797836767
JSON

Presynaptic and preterminal nAChRs increase the release of neurotransmitters in the hippocampus, particularly the main neurotransmitters, GABA and glutamate (41, 78, 81, 97).

p(FPLX:CHRN) increases bp(GO:"neurotransmitter secretion") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Presynaptic Terminals

p(FPLX:CHRN) increases sec(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Presynaptic Terminals

p(FPLX:CHRN) increases sec(a(CHEBI:"gamma-aminobutyric acid")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Presynaptic Terminals

Evidence 4d8589b00a
JSON

Furthermore, by directly exciting or by shunting the progress of an action potential at a bifurcation, axonal or dendritic nAChRs alter the spread of neuronal excitation.

p(FPLX:CHRN) regulates bp(GO:"rhythmic excitation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Axons
MeSH
Dendrites

Evidence 5bb419270d
JSON

Nicotinic stimulation enhances glutamate release on multiple timescales, extending from seconds to a few minutes (81), and contributes to the induction of synaptic plasticity (4, 13, 14, 16, 88).

act(p(FPLX:CHRN)) increases bp(GO:"regulation of synaptic plasticity") View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) increases sec(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Appears in Networks:

Evidence 7a59f0e649
JSON

Decline, disruption, or alterations of nicotinic cholinergic mechanisms have been implicated in various dysfunctions, such as schizophrenia, epilepsy, autism, Alzheimer’s disease (AD), and addiction (17–23).

p(FPLX:CHRN) association path(MESH:Schizophrenia) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:Epilepsy) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:"Autistic Disorder") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) association path(MESH:"Behavior, Addictive") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:"Autistic Disorder") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:"Behavior, Addictive") association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:Epilepsy) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:Schizophrenia) association p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

Evidence b7c155798f
JSON

Nicotinic mechanisms contribute to cognitive function, and the decline of nicotinic mechanisms or loss of nAChRs has been observed in AD, dementia with Lewy bodies, Down syndrome, autism, and Parkinson’s disease (20, 140).

act(p(FPLX:CHRN)) negativeCorrelation path(MESH:"Autistic Disorder") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) negativeCorrelation path(MESH:"Autistic Disorder") View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) negativeCorrelation path(MESH:"Lewy Body Disease") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) negativeCorrelation path(MESH:"Lewy Body Disease") View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) negativeCorrelation path(MESH:"Down Syndrome") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) negativeCorrelation path(MESH:"Down Syndrome") View Subject | View Object

Appears in Networks:

act(p(FPLX:CHRN)) negativeCorrelation path(MESH:"Parkinson Disease") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) negativeCorrelation path(MESH:"Parkinson Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:"Autistic Disorder") negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

path(MESH:"Autistic Disorder") negativeCorrelation p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:"Down Syndrome") negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

path(MESH:"Down Syndrome") negativeCorrelation p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:"Lewy Body Disease") negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

path(MESH:"Lewy Body Disease") negativeCorrelation p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

path(MESH:"Parkinson Disease") negativeCorrelation act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

path(MESH:"Parkinson Disease") negativeCorrelation p(FPLX:CHRN) View Subject | View Object

Appears in Networks:

Evidence dca06ace4f
JSON

Mammalian nAChRs are cation selective, being permeable to small monovalent and divalent cations.

p(FPLX:CHRN) increases tloc(a(MESH:"Cations, Monovalent"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) increases tloc(a(MESH:"Cations, Monovalent"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) increases tloc(a(MESH:"Cations, Divalent"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) increases tloc(a(MESH:"Cations, Divalent"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

Appears in Networks:

Evidence f8003fef67
JSON

Nicotinic receptor activity causes depolarization, and the divalent cation perme- ability plays an important physiological role by supplying ionic signals, including calcium (39–41).

act(p(FPLX:CHRN)) increases bp(GO:"membrane depolarization") View Subject | View Object

Appears in Networks:

Evidence 78f8f8ebc8
JSON

Activation of nAChRs on distal apical dendrites depolarizes the cell and promotes action potential firing

act(p(FPLX:CHRN)) increases bp(GO:"membrane depolarization") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendrites
MeSH
Neocortex

act(p(FPLX:CHRN)) increases bp(GO:"regulation of action potential firing rate") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendrites
MeSH
Neocortex

Evidence f1bdfeb187
JSON

Nicotinic receptors mediate a small direct calcium influx (42–44, 85).

act(p(FPLX:CHRN)) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Appears in Networks:

Evidence 66db0278e0
JSON

Furthermore, Src-family kinases (SFKs) directly phosphorylate the cytoplasmic loop of α7 nAChRs in the plasma membrane.

act(p(FPLX:SRC), ma(kin)) increases p(HGNC:CHRNA7, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cell Membrane

Evidence 1be9d93c47
JSON

A mutation in the gene encoding the α4 nAChR subunit (CHRNA4) causes a genetically transmissible form of epilepsy, which was the first discovery of a human disease associated with a neuronal nAChR (165, 166). The mutation has been identified as a single base substitution converting a serine into threonine (S248F) in the TM2 domain of the α4 subunit (165).

p(HGNC:CHRNA4, var("p.Ser248Thr")) increases path(MESH:Epilepsy) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Epilepsy

Evidence eed996d4b3
JSON

Similarly, replacement of the α7 leucine at the synaptic, extracellular end (position 254 or 255) of the pore by threonine dramatically reduced the calcium permeability of the α7 receptors.

p(HGNC:CHRNA7, var("p.Leu254Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu254Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu255Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu255Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

Appears in Networks:

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.