Distribution of Nicotinic Receptors in the CNS

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Abstract
The original classification of cholinergic receptors into two classes (muscarinic and nicotinic), based on drug interactions, indicated the key importance of nicotinic receptors (nAchRs) at the muscle end plate and a preponderance of muscarinic receptors (mAchRs) in the central nervous system (CNS). However, recent findings suggest that although brain nAchRs are less numerous than mAchRs they are likely to have an important role in behavior and cognition, 1–6 are affected by aging and dementia (see below), and may have neurotrophic and neuroprotective functions. 7–10 CNS nAchRs are a family of ligand-gated cation channels, with a pentameric structure generally comprised of two alpha and three beta subunits. 11–14 Pharmacological studies have suggested heterogeneity of this class of cholinergic receptor in the brain (more than one binding site for nicotine 15 and subpopulations with varying agonist and antagonist sensitivity 16–20 ), and this has been confirmed by more recent molecular biological techniques, largely conducted on brain from rodent (see below) and chick. 21 In the rat at least six alpha subunits (α2, α3, α4, α5, α6, α7) and three beta subunits (β2, β3, β4) have been identified, and different subunit composition appears to result in distinct, although not exclusive, receptor pharmacological profiles (for reviews see References 11, 12, 19, and 22). Although it is the a subunit that possesses the agonist binding site, it has become clear that the β composition of the receptor may also affect the ligand specificity and rate of desensitization of receptor subtypes. 11 , 23–25

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