Evidences a(CHEBI:nicotine) to p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")

The other subtype of AChR is the fast ionotropic cationic nicotinic receptor channel (nAChR). These receptors are sensitive to activation by nicotine and have ion channels whose activity is induced in the micro- to submicrosecond range.

Also, the continuous exposure of cells to nicotine increases nAChR surface expression by reducing degradation of the intracellular pool of receptors (367, 394).

In the smoker’s brain, upregulation can increase high-affinity nicotine binding by nearly fourfold relative to age- and gender-matched controls that have not been exposed to nicotine (373, 421). The mechanism by which nicotine increases the total number of high-affinity nAChRs, though poorly defined, is highly conserved among species.

Mechanistically, nicotine, acting through nAChRs, decreases keratinocyte migration (188, 189) and modifies the activity of PI3K/Akt, ERK, MEK, and JAK signaling pathways.

First, age-related nAChR subunit expression decline was observed in both strains, and this was dominated by diminished alpha4 nAChR expression. Second, long-term (12 mo) oral nicotine failed to reduce the age-related decline in the number of neurons expressing alpha4 nAChR subunits, although the neurons that remained exhibited larger processes with more varicosities than age-matched controls (165, 396). Acute nicotine treatment (alpha6 wk of oral nicotine) of aged mice had no measurable influence on nAChR expression, neuronal viability, or dendritic complexity (e.g., Ref. 396)

Nicotine is perhaps the most addictive drug that is widely used; 95% or more of its users with a strong desire to stop using it relapse within 1 yr (47, 203). Chronic nicotine use and the phenotypes of addiction are closely associated in humans and other animals with concurrent physiological changes in nAChR function and expression

The discovery that nicotine, a ligand acting at nAChRs, and its mimetics can protect neurons against Abeta toxicity (Kihara et al., 1998) is of interest, especially in view of the observation that nicotine also enhances cognition (Rusted et al., 2000). Nicotinic receptors play a particularly prominent role in nicotine protection. The protective effect is blocked by the nicotinic antagonists dihydro-beta-erythroidine and mecamylamine (Kihara et al., 2001; Takada- Takatori et al., 2006).

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).

Chronic exposure to nicotine causes a striking increase, typically by twofold, in the total number of high-affinity receptors — a process termed upregulation8.

Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156).

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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.