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Appears in Networks 12

In-Edges 21

complex(a(MESH:methyllycaconitine), p(HGNC:CHRNA3)) decreases act(p(HGNC:CHRNA3, loc(MESH:Muscles))) View Subject | View Object

Finally, the alkaloid methyllycaconitine (MLA) emerged as a potent and specific competitive antagonist that inhibits muscle, alpha7-, alpha6-, and alpha3-containing nAChRs (30, 326, 445). The alkaloid is derived from the larkspur (genus Delphinium), which is of great economic interest since estimates of its cost to ranchers in poisoned livestock exceeds many millions of dollars annually. Similar to most nAChR poisons, MLA binds to the receptor agonistbinding site (Fig. 3) in a manner similar to that of alpha-BGT to block agonist binding and receptor activation. PubMed:19126755

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a(CHEBI:"amyloid-beta") increases p(HGNC:CHRNA3) View Subject | View Object

Similar effects of Abeta on nAChR expression have been confirmed in studies using cultured cells; Abeta causes a reduced expression of nAChRs in PC12 cells (Guan et al., 2001), and alpha4, alpha3, and alpha7 expression are all increased in cultured rat astrocytes (Xiu et al., 2005). PubMed:19293145

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA3) View Subject | View Object

However, a reduction of alpha3 subunits in a Western blot analysis of brains from patients with AD has been observed (Guan et al., 2000), although the loss was not as great as that observed for alpha4 or alpha7 subunits. In addition, alpha3 subunit levels were reduced in the temporal cortex and hippocampus of brains from patients with AD, both smokers and nonsmokers, compared with control subjects (Mousavi et al., 2003). PubMed:19293145

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA3) View Subject | View Object

Thus, predominantly alpha4 and alpha7 subunits, and to a lesser extent alpha3 subunits, are lost in AD, although there are tissue-specific differences to this pattern, such as the upregulation of nAChRs on astrocytes. PubMed:19293145

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA3) View Subject | View Object

Thus, in brains from patients with AD and in neurons responding to exogenously applied Abeta, there is a reduction in expression of nAChR subunits, especially alpha4, alpha7, beta4, and possibly alpha3. Although AD may also involve changes in expression of other ligand-gated ion channels— for example, the expression of NMDA receptors (Bi and Sze, 2002; Jacob et al., 2007), alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptors (Jacob et al., 2007), and beta3 GABA receptor subunits are all reduced (Mizukami et al., 1998)—there is abundant evidence of a loss of nAChR subunits in AD possibly caused by the actions of Abeta. PubMed:19293145

complex(p(HGNC:CHRNA3), p(HGNC:LYNX1)) regulates act(p(HGNC:CHRNA3)) 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

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA3) View Subject | View Object

When the laminar binding distribution of [3H]nicotine, [3H]epibatidine, and [3H]cytisine was measured in AD cortical autopsy tissue, marked reductions were observed relative to control brains (Sihver et al 1999c) (Figure 1) PubMed:11230871

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA3) View Subject | View Object

A decrease in the protein levels of the alpha3 and alpha4 nAChR subunits was recently measured in the temporal cortex and of the alpha3, alpha4, and alpha7 nAChR subtypes in the hippocampi of AD brains relative to age-matched control subjects (Guan et al 2000b) PubMed:11230871

path(MESH:Craving) association p(HGNC:CHRNA3) View Subject | View Object

β4 deletion abolishes withdrawal signs in the mouse208, and α3 and β4 are also present in the PNS, supporting the view that they might be directly involved in craving and relapse — an area that is largely unexplored in the development of medications to assist with smoking cessation. PubMed:19721446

path(MESH:Recurrence) association p(HGNC:CHRNA3) View Subject | View Object

β4 deletion abolishes withdrawal signs in the mouse208, and α3 and β4 are also present in the PNS, supporting the view that they might be directly involved in craving and relapse — an area that is largely unexplored in the development of medications to assist with smoking cessation. PubMed:19721446

bp(HBP:"habenulo-interpeduncular pathway") increases p(HGNC:CHRNA3, loc(MESH:"Central Nervous System")) View Subject | View Object

The Hb-IPN system expresses the highest levels and va- riety of nAChR subunits and subtypes in mammalian brain [85], and is the only central system expressing high levels of α3, β4 and α5 subunits. PubMed:28901280

Out-Edges 6

p(HGNC:CHRNA3) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

On the other hand, neuronal nicotinic receptors are formed by the combination of only two types of subunits (α2-10 and β2-4) PubMed:26813123

p(HGNC:CHRNA3) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

When the laminar binding distribution of [3H]nicotine, [3H]epibatidine, and [3H]cytisine was measured in AD cortical autopsy tissue, marked reductions were observed relative to control brains (Sihver et al 1999c) (Figure 1) PubMed:11230871

p(HGNC:CHRNA3) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A decrease in the protein levels of the alpha3 and alpha4 nAChR subunits was recently measured in the temporal cortex and of the alpha3, alpha4, and alpha7 nAChR subtypes in the hippocampi of AD brains relative to age-matched control subjects (Guan et al 2000b) PubMed:11230871

p(HGNC:CHRNA3) association path(MESH:Craving) View Subject | View Object

β4 deletion abolishes withdrawal signs in the mouse208, and α3 and β4 are also present in the PNS, supporting the view that they might be directly involved in craving and relapse — an area that is largely unexplored in the development of medications to assist with smoking cessation. PubMed:19721446

p(HGNC:CHRNA3) association path(MESH:Recurrence) View Subject | View Object

β4 deletion abolishes withdrawal signs in the mouse208, and α3 and β4 are also present in the PNS, supporting the view that they might be directly involved in craving and relapse — an area that is largely unexplored in the development of medications to assist with smoking cessation. PubMed:19721446

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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.