In terms of functional effects, nicotine acts acutely much in the way that ACh does, causing opening of nAChR channels.
There is an emerging consensus that nAChR a6 subunit mRNA and proteins are distributed in brain regions thought to be involved in reward and drug reinforcement, in theory being involved in DA release [135].
Also, Endo et al. [141] found naturally-expressed a3b2- and a6b2-nAChRs on superior colli- culus neurons, and these receptors are likely located on pre- synaptic terminals of GABAergic neurons where they modulate GABA release.
b4 subunit mRNA colocalizes with a4 subunit mRNA in many brain regions [37,38] that could be involved in complex behaviors including nicotine dependence.
a6 subunits are not widely expressed in the brain, but they are prevalent in midbrain dopaminergic (DAergic) regions associated with pleasure, reward, and mood control
Recently, we reported a novel discovery that functional a6*-nAChRs are located on GABAergic presynaptic boutons associated with VTA DAergic neurons, where these a6*- nAChRs mediate nicotinic modulation of GABA release onto those DAergic neurons [122].
This makes the hypothesis particularly intriguing that a6*-nAChRs play roles in nicotine dependence.
There is good evidence that a6*-nAChRs, in particular, modulate neurotransmitter release in multiple brain regions.
Subsequently, renewed searches for functions of natural Bgt-binding nAChRs uncovered short-lived, nicotine-gated, toxin-sensitive, inward currents and/ or elevations of intracellular Ca2+ in chick autonomic neurons [84], in human ganglionic neuron-like clonal cells [85], or in rat CNS neurons [16,40–44,86–91].
By virtue of their unique subcellular localizations, channel kinetics and Ca2+ permeability, a7-nAChRs appear to have novel functional roles in addition to (i.e., distinct from) the mediation of classical excitatory neurotransmission.
For example, Bgt-sensitive a7-nAChRs have been implicated in processes such as vicinal control of neurotransmitter release [7,14], development and maintenance of neurites and synapses [18–20], long-term potentiation [95,96], seizures [97], and neuronal viability/death [21–24]. These intriguing findings underscore the need for further characterization of functional a7-nAChRs.
Other ‘‘a3b2-specific’’ antagonists, such as neuronal- or kappa- bungarotoxin and a-CtxPnIA, have also turned out to block a6*- nAChRs [129].
a4b2-nAChRs have been implicated in nicotine self-administration, reward, and depen- dence, and in diseases such as Alzheimer’s and epilepsy [1–5,27–33].
Initially, a-CtxMII was thought to be highly selective for a3b2*-nAChRs [124] and became a useful tool for investigating receptor structure [125].
Moreover, some nAChRs have been implicated in processes such as the structuring and maintenance of neurites and synapses [18–20] and even in modulation of neuronal viability/death [21–24].
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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.