a(HBP:"alpha-4-containing nAChR")
In summary, while nicotine-induced upregulation requires at least the beta2 nAChR subunit, development of tolerance to nicotine requires neither the beta2 nor the alpha7 nAChR subunit; instead, it appears to be modulated by a beta4-containing nAChR and to require an alpha4-containing nAChR. PubMed:19126755
While chronic nicotine does not change the abundance or function of alpha4* nAChRs in the somata of substantia nigra pars compacta dopaminergic neurons, it does suppress baseline firing rates of these DA neurons. PubMed:21482353
These contrasting effects on GABA and DA neurons are due to upregulated alpha4* nAChR responses in GABA neurons, at both somata and synaptic terminals PubMed:21482353
Chronic nicotine upregulates alpha4* nAChRs in dopaminergic presynaptic terminals, apparently leading to increased resting dopamine release from those terminals PubMed:21482353
The chaperoning of nAChRs by nicotine enhances the export of alpha4beta2 nAChRs from the endoplasmic reticulum (ER), and this leads to a general increase in ER exit sites (Srinivasan et al., 2011) PubMed:21482353
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
A decrease in protein levels of the alpha4 nAChR but not of the alpha3 and alpha7 nAChRs was reported by Martin-Ruiz et al (1999) PubMed:11230871
Interestingly, a reduction in the protein level of alpha7 has also been measured in the frontal cortex of patients with schizophrenia (Guan et al 1999), whereas no decrease was measured in the alpha4 nAChR protein level (Guan et al 1999) PubMed:11230871
In summary, while nicotine-induced upregulation requires at least the beta2 nAChR subunit, development of tolerance to nicotine requires neither the beta2 nor the alpha7 nAChR subunit; instead, it appears to be modulated by a beta4-containing nAChR and to require an alpha4-containing nAChR. PubMed:19126755
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
A decrease in protein levels of the alpha4 nAChR but not of the alpha3 and alpha7 nAChRs was reported by Martin-Ruiz et al (1999) PubMed:11230871
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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.