Neuronal nicotinic acetylcholine receptor function

Paton WDM, Zaimis EJ (1949) The pharmacological actions of polymethylene bistrimethylammo-nium salts. Br J Pharmacol Chemother 4 381 00 Patrick J, Stallcup WB (1977) a-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line. J Biol Chem 252 8629-8633 Patrick J, Boulter J, Deneris E, Wada K, Wada E, Connolly J, Swanson L, Heinemann S (1989) Structure and function of neuronal nicotinic acetylcholine receptors deduced from cDNA clones. Prog Brain Res 79 27-33... 

Inhaled nicotine is efficiently delivered to the brain (see chapter by Benowitz, this volume) where it selectively interacts with its central targets, the neuronal nicotinic acetylcholine receptors (nAChRs). The multiple subtypes of uAChR (see chapter by Collins et al, this volume) all bind nicotine but with different affinities, depending on the subunit composition of the uAChR. Binding may result in activation or desensitisation of uAChRs, reflecting the temporal characteristics of nicotine dehvery and local concentration of nicotine. Another level of complexity of the actions of nicotine reflects the widespread and non-uniform distribution of uAChR subtypes within the brain, such that nicotine can influence many centrally regulated functions in addition to the reward systems. In this chapter, we address the consequences of nicotine interactions with nAChRs at the molecular, cellular and anatomical levels. We critically evaluate experimental approaches, with respect to their relevance to human smoking, and contrast the acute and chronic effects of nicotine. 

Buisson B, Bertrand D (2001) Chronic exposure to nicotine upregulates the human alpha4beta2 nicotinic acetylcholine receptor function. J Neurosci 21 1819-1829 CeUe PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK (2004) Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41 907-914... 

Antibodies specific for neuronal nicotinic acetylcholine receptors in the autonomic ganglia have been identified in some patients with both idiopathic and paraneoplastic autonomic neuropathy, and high levels of these antibodies were correlated with more severe disease, suggesting that the antibodies may be of functional importance [108],... 

Briggs CA, Anderson DJ, Brioni JD, Buccafusco JJ, Buckley MJ, et al. 1996. Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo. Pharmacol Biochem Behav 57 231-241. 

Abstract The existence of neuronal nicotinic acetylcholine receptor (nAChRs) expression in the brain was discovered 30 years ago. Although the relevance of neuronal nAChRs at the time of their discovery was debated, it is now clear that nAChRs are expressed throughout the brain where they mainly serve a modulatory role. Neuronal nAChRs increasingly have become of interest due to the many observations that various nAChR subtypes exhibit abnormal expression or function in a wide assortment of neurological diseases. In this review, the putative role of nAChRs in brain disease is discussed in several broad categories (1) diseases associated with a loss of nAChRs, (2) diseases associated with innate differences in the expression of nAChRs, (3) diseases associated with genetic variability in genes that code for nAChR subunit proteins, and (4) diseases in which nAChRs are implicated based on the observation that nicotine has a therapeutic effect. 

Deneris ES, Conolly J, Rogers SW, Duvoisin R (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors. Trends Pharmacol Sci, 12, 34-40. 

Duvoisin RM, Deneris ES, Patrick J, Heinemann S (1989) The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit beta 4. Neuron, 3, 487-496. 

A. Nicke, S. Wonnacott, R.J. Lewis, a-Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes, Eur.J. Biochem. 2004, 271, 2305-2319. 

Coleridge JCG, Coleridge HM (1984) Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev Physiol Biochem Pharmacol 99 1-110 Colquhoun LM, Patrick JW (1997) Pharmacology of neuronal nicotinic acetylcholine receptor subtypes. Adv Pharmacol 39 191-220... 

Albuquerrque EX, Alkondon M, Pereira EFR (1996) Properties of neuronal nicotinic acetylcholine receptors pharmacological characterization and modulation of synaptic function. J Pharmacol Exp Ther 280 1117... 

These include nicotinic acetylcholine receptors, neuronal calcium channels, muscle sodium channels, vasopressin receptors, and iV-methyl-D-aspartate (NMDA) receptors. Some general features of the structure, function, and evolution of biologically active peptides isolated from Conus venom are presented. 

Karlin, A., Akabas, M.H. Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins. Neuron. 15 1231, 1995. 

Gentry CL, Lukas RJ (2002) Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure. Curr Drug Targets CNS Neurol Disord 1 359-385 Gerzanich V, Wang F, Kuryatov A, Lindstrom J (1998) Alpha 5 subunit alters desensitization, pharmacology, Ca++ permeability and Ca++ modulation of human neuronal alpha 3 nicotinic receptors. J Pharmacol Exp Ther 286 311-320... 

Hann, et al. Tobacco cembranoids block behavioral sensitization to nicotine and inhibit neuronal acetylcholine receptor function. J Neurosci Res... 

Pereira, E.F.R. et ah. Identification and functional characterization of a new agonist site on nicotinic acetylcholine receptors of cultured hippocampal neurons, J. Pharmacol. Exp. Ther., 265, 1474, 1993. 

Steinbach, J.H. "Activation of nicotinic acetylcholine receptors" Cotman, C.W., Poste, G. Nicholson, G.L. Eds. Cell surface and neuronal function, Elsevier/North Holland, New York, 1980, p.119-151. 

Recent data indicate that AEA can interact with known GPCRs for other neuronal mediators or with novel GPCRs. AEA was found to exhibit inhibitory activity on 5-hydroxy-tryptamine receptors (Kimura et al., 1998), and both muscarinic and nicotinic acetylcholine receptors (Lagalwar et al., 1999 Oz et al., 2003). Except for the inhibitory effect on nACh alpha7 nicotinic receptors (IC50 = 218 wM), however, AEA appears to modulate the binding and functional activity of 5-HT and acetylcholine only at concentrations (> 5 iM) that are not likely to occur in vivo. Regarding... 

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