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a(HBP:"alpha-4 beta-2 nAChR")

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Entity

Name
alpha-4 beta-2 nAChR
Namespace
HBP
Namespace Version
20181221
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/bd0996a28201cad363557315043c6392e31abf58/export/hbp-names.belns

Appears in Networks 6

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

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

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

Up-regulation of Nicotinic Receptors by Nicotine Varies with Receptor Subtype v1.0.0

In-Edges 23

a(CHEBI:"dihydro-beta-erythroidine") decreases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Nicotine protection of cultured rat cortical neu- rons against Abeta toxicity is blocked by the alpha4beta2 antagonist, dihydro-beta-erythroidine (Kihara et al., 1998). PubMed:19293145

Appears in Networks:

path(MESH:"Alzheimer Disease") association a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

Genetic association studies investigating single nucleotide polymorphisms point to roles for cholinergic signaling components such as the synthetic enzyme ChAT, the inactivating enzyme AChE, and alpha4beta2 nAChRs in AD (Cook et al., 2004, 2005; Vasto et al., 2006). The most vulnerable neurons in AD seem to be those expressing high levels of nAChRs, particularly those containing the alpha7 subunit (D’Andrea and Nagele, 2006), and the numbers of nAChRs as well as some of their associated proteins change in AD (Martin-Ruiz et al., 1999; Gotti et al., 2006; Sabbagh et al., 2006). PubMed:19293145

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 40") decreases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Experiments performed on X. laevis oocytes transiently transfected with alpha7 or alpha4beta2 cDNA showed a concentration dependent effect of Abeta on receptor inhibition. In this case the peptide used was Abeta1-40 and the concentrations adopted were between 0.1 and 10 mM, with increased Abeta concentration resulting in a bigger inhibition of the receptor (Tozaki et al., 2002) PubMed:25514383

Appears in Networks:
Annotations
Cell Ontology (CL)
oocyte

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Further studies showed an inhibitory effect of Abeta1-42 on human alpha4beta2 nAChRs transfected in the cell line (SHEP1) (Wu et al., 2004) PubMed:25514383

Appears in Networks:

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

Appears in Networks:
Annotations
Cell Ontology (CL)
oocyte

bp(GO:"calcium ion transport") negativeCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

The subtype alpha4beta2 is characterized by lower calcium ion permeability and a slow desensitization rate compared to the homopentameric alpha7 nAChR (Quick and Lester, 2002) PubMed:25514383

Appears in Networks:

complex(p(HGNC:CHRNA4), p(HGNC:CHRNB2)) increases a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

This subunit commonly forms heteropentameric receptors in combination with the alpha4 subunit PubMed:25514383

Appears in Networks:

composite(a(CHEBI:"amyloid-beta"), a(CHEBI:nicotine)) increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Arora et al. (2013) investigated, in a cellular system, the effect of prolonged Abeta exposure on nAChR function. The rodent neuroblastoma cell line NG108-15 was transfected with alpha4beta2 nAChRs and treated for three days with 100 nM Abeta. The following acute stimulation with Abeta and nicotine led to receptor activation that caused a perturbation of intracellular calcium homeostasis followed by mitochondrial dysfunction and increased oxidative stress (Arora et al., 2013) PubMed:25514383

Appears in Networks:

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

In the medial perforant path, which mainly arises from layer II stellate cells, chronic nicotine upregulates alpha4beta2* nAChRs PubMed:21482353

Appears in Networks:
Annotations
MeSH
Dentate Gyrus
MeSH
Entorhinal Cortex

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

In midbrain, chronic nicotine treatment elicits a general increase in alpha4beta2* nAChRs in GABAergic neurons, but only in axon terminals of DA neurons PubMed:21482353

Appears in Networks:
Annotations
MeSH
GABAergic Neurons
MeSH
Mesencephalon

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

Because alpha4beta2 nAChRs are the most susceptible to nicotine-induced upregulation, the data again seem consistent with the idea that selective upregulation of alpha4beta2 nAChRs underlies nicotine dependence PubMed:21482353

Appears in Networks:

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

The upregulation of alpha4beta2* nAChRs by chronic nicotine treatment has been replicated many times in numerous systems—transfected cell lines, neurons in culture, brain slices, and smokers’ brains (Albuquerque et al., 2009; Fu et al., 2009; Lester et al., 2009; Srinivasan et al., 2011 PubMed:21482353

Appears in Networks:

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

(3) Nicotine activates alpha4beta2 nAChRs ~400-fold more effectively than it activates muscle-type nAChRs, because of cation-π and H-bond interactions at the agonist binding site (Xiu et al., 2009) PubMed:21482353

Appears in Networks:

a(MESH:"Dopaminergic Neurons") positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

In the midbrain, both DA neurons (in substantia nigra pars compacta and ventral tegmental area [VTA]) and GABAergic neurons (in substantia nigra pars reticulata and VTA) express high levels of alpha4beta2* nAChRs on their somata, but only GABAergic neurons display somatic upregulation (Nashmi et al., 2007; Xiao et al., 2009) PubMed:21482353

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Compacta
MeSH
Ventral Tegmental Area

a(MESH:"GABAergic Neurons") positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

In the midbrain, both DA neurons (in substantia nigra pars compacta and ventral tegmental area [VTA]) and GABAergic neurons (in substantia nigra pars reticulata and VTA) express high levels of alpha4beta2* nAChRs on their somata, but only GABAergic neurons display somatic upregulation (Nashmi et al., 2007; Xiao et al., 2009) PubMed:21482353

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Reticulata
MeSH
Ventral Tegmental Area

bp(GO:cognition) positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

In rodents and humans, the hippocampus is importantly implicated in cognitive sensitization, and alpha4beta2* nAChRs play key roles (Levin et al., 2006; Davis and Gould, 2009) PubMed:21482353

Appears in Networks:

complex(a(HBP:"alpha-4 beta-2 nAChR"), p(HGNC:LYNX1)) hasComponent a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

Appears in Networks:

complex(a(HBP:"alpha-4 beta-2 nAChR"), p(HGNC:LYNX1)) regulates act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Each lynx paralog has a relative binding specificity and modulatory capability on alpha4beta2 (Miwa et al., 1999; Iban˜ ez-Tallon et al., 2002; Levitin et al., 2008), alpha3 (Arredondo et al., 2006), and alpha7 (Chimienti et al., 2003; Levitin et al., 2008; Hruska et al., 2009) nAChR subtypes; some interactions actually enhance nicotinic responses (Chimienti et al., 2003; Levitin et al., 2008), or their Ca2+ components (Darvas et al., 2009) PubMed:21482353

Appears in Networks:

composite(a(HBP:"alpha-4 beta-2 nAChR"), p(HGNC:LYNX1)) hasComponent a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

Appears in Networks:

path(MESH:"Tobacco Use Disorder") increases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Because alpha4beta2 nAChRs are the most susceptible to nicotine-induced upregulation, the data again seem consistent with the idea that selective upregulation of alpha4beta2 nAChRs underlies nicotine dependence PubMed:21482353

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

A ligand with a selectivity for the alpha4beta2 nAChRs would be particularly preferable because the alpha4beta2 has been recognized as the predominant subtype that is deficient in AD (for a review, see Sihver et al 2000) PubMed:11230871

Appears in Networks:

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

This range is broader but similar to what was observed for a4b2 where the -fold increase after nicotine treat- ment varied 3–6-fold (29). PubMed:18174175

Appears in Networks:

complex(a(CHEBI:epibatidine), a(HBP:"alpha-4 beta-2 nAChR")) hasComponent a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

Appears in Networks:

Out-Edges 9

act(a(HBP:"alpha-4 beta-2 nAChR")) decreases act(a(MESH:Interneurons)) View Subject | View Object

On the other hand, when alpha4beta2 nAChRs are activated, both SR and SLM interneurons are inhibited, resulting in disinhibition of dendritic areas innervated by both neuron types. PubMed:19126755

Appears in Networks:
Annotations
Uberon
hippocampus stratum lacunosum moleculare
Text Location
Review

a(HBP:"alpha-4 beta-2 nAChR") association path(MESH:"Alzheimer Disease") View Subject | View Object

Genetic association studies investigating single nucleotide polymorphisms point to roles for cholinergic signaling components such as the synthetic enzyme ChAT, the inactivating enzyme AChE, and alpha4beta2 nAChRs in AD (Cook et al., 2004, 2005; Vasto et al., 2006). The most vulnerable neurons in AD seem to be those expressing high levels of nAChRs, particularly those containing the alpha7 subunit (D’Andrea and Nagele, 2006), and the numbers of nAChRs as well as some of their associated proteins change in AD (Martin-Ruiz et al., 1999; Gotti et al., 2006; Sabbagh et al., 2006). PubMed:19293145

Appears in Networks:

a(HBP:"alpha-4 beta-2 nAChR") negativeCorrelation bp(GO:"calcium ion transport") View Subject | View Object

The subtype alpha4beta2 is characterized by lower calcium ion permeability and a slow desensitization rate compared to the homopentameric alpha7 nAChR (Quick and Lester, 2002) PubMed:25514383

Appears in Networks:

act(a(HBP:"alpha-4 beta-2 nAChR")) decreases bp(GO:"cellular calcium ion homeostasis") View Subject | View Object

Arora et al. (2013) investigated, in a cellular system, the effect of prolonged Abeta exposure on nAChR function. The rodent neuroblastoma cell line NG108-15 was transfected with alpha4beta2 nAChRs and treated for three days with 100 nM Abeta. The following acute stimulation with Abeta and nicotine led to receptor activation that caused a perturbation of intracellular calcium homeostasis followed by mitochondrial dysfunction and increased oxidative stress (Arora et al., 2013) PubMed:25514383

Appears in Networks:

act(a(HBP:"alpha-4 beta-2 nAChR")) increases path(HBP:"mitochondrial dysfunction") View Subject | View Object

Arora et al. (2013) investigated, in a cellular system, the effect of prolonged Abeta exposure on nAChR function. The rodent neuroblastoma cell line NG108-15 was transfected with alpha4beta2 nAChRs and treated for three days with 100 nM Abeta. The following acute stimulation with Abeta and nicotine led to receptor activation that caused a perturbation of intracellular calcium homeostasis followed by mitochondrial dysfunction and increased oxidative stress (Arora et al., 2013) PubMed:25514383

Appears in Networks:

act(a(HBP:"alpha-4 beta-2 nAChR")) increases bp(GO:"response to oxidative stress") View Subject | View Object

Arora et al. (2013) investigated, in a cellular system, the effect of prolonged Abeta exposure on nAChR function. The rodent neuroblastoma cell line NG108-15 was transfected with alpha4beta2 nAChRs and treated for three days with 100 nM Abeta. The following acute stimulation with Abeta and nicotine led to receptor activation that caused a perturbation of intracellular calcium homeostasis followed by mitochondrial dysfunction and increased oxidative stress (Arora et al., 2013) PubMed:25514383

Appears in Networks:

a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation bp(GO:cognition) View Subject | View Object

In rodents and humans, the hippocampus is importantly implicated in cognitive sensitization, and alpha4beta2* nAChRs play key roles (Levin et al., 2006; Davis and Gould, 2009) PubMed:21482353

Appears in Networks:

a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation a(MESH:"Dopaminergic Neurons") View Subject | View Object

In the midbrain, both DA neurons (in substantia nigra pars compacta and ventral tegmental area [VTA]) and GABAergic neurons (in substantia nigra pars reticulata and VTA) express high levels of alpha4beta2* nAChRs on their somata, but only GABAergic neurons display somatic upregulation (Nashmi et al., 2007; Xiao et al., 2009) PubMed:21482353

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Compacta
MeSH
Ventral Tegmental Area

a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation a(MESH:"GABAergic Neurons") View Subject | View Object

In the midbrain, both DA neurons (in substantia nigra pars compacta and ventral tegmental area [VTA]) and GABAergic neurons (in substantia nigra pars reticulata and VTA) express high levels of alpha4beta2* nAChRs on their somata, but only GABAergic neurons display somatic upregulation (Nashmi et al., 2007; Xiao et al., 2009) PubMed:21482353

Appears in Networks:
Annotations
MeSH
Mesencephalon
MeSH
Pars Reticulata
MeSH
Ventral Tegmental Area

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