Neuronal nicotinic acetylcholine receptors activation

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. 

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Bannon, A. W., Decker, M. W., Holladay, M. W., Curzon, P., Donnelly-Roberts, D. L., Puttfarcken, P. S., Bitner, R. S., Diaz, A., Dickenson, A. H., Porsolt, R. D., Williams, M., Arneric, S. P. Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors, Science 1998, 279, 77-81. 

Bannon AW, Decker MW, Holladay MW, Curzon P, Donnelly-Roberts D, Puttfarcken PS, Bitner RS, Diaz A, Dickenson AH, Porsolt RD, Wilhams M, Arneric SP (1998) Broad-spectrum, nonopioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science 279 77-81... 

Nicolotti, O., Pellegrini-Calace, M., Altomare, C., Carotti, A., Carrieri, A., and Sanz, F. 2002. Ligands of neuronal nicotinic acetylcholine receptor (nAChR) Inferences from the Hansch and 3-D quantitative structure-activity relationship... 

Nicotine is an agonist to the neuronal nicotinic acetylcholine receptors (nAChR). These receptors are the likely site at which nicotine exerts its central actions. Evidence supports the involvement of the central nAChR in neurotransmitter release (195), and a large body of evidence indicates that dopamine release from dopaminergic neurons is mediated by activation of the brain nAChRs (196). It has also been shown that both nicotinic receptors and muscarinic receptors in the ventral tegmental area (VTA) activate the dopaminergic neurons and thus play a role in the reward effect of nicotine (197). In addition, animal data sug-... 

M., Briggs, C.A., Williams, M., Americ, S.P., 1998. Identification and initial stmcture-activity relationships of (J )-5-(2-Azetidinyl-methoxy)-2-chlorpyridine (ABT-594), a potent, orally active, nonopiate analgesic agent acting via neuronal nicotinic acetylcholine receptors. J. Med. Chem. 41, 407-412. 

The cholinergic system in insects is the main target of insecticides. One class of molecules, the neonicotinoids, induces direct activation of the neuronal nicotinic acetylcholine receptors (nAChRs). In the honey bee these receptors are mainly distributed in the olfactory pathways that link sensory neurons to antennal lobes and mushroom bodies. These structures seem to play an important role in olfactory conditioning. We have previously shown that cholinergic antagonists injected in different parts of the brain impaired the formation and retrieval of olfactory memory. We then advanced the hypothesis that, through the activation of the nAChR, the neonicotinoid imidacloprid (IMI) would lead to facilitation of the memory trace. 

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Chiodini F, Charpantier E, Muller D, et al. Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 94 643-651. 

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. 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR). Activation of this receptor depolarizes target cells (see Ch. 11). nAChRs are composed of five subunits surrounding a central ion-channel pore. Twelve different nicotinic receptor subunits are expressed in the nervous system (a2-oclO and (32—134). Of these, a subset is expressed in the VTA (a3-a7 and P2—134). It is thought that a7 receptors form homomeric receptors a3, a4 and a6 form heteromeric channels with 02 or 04 and a5 and 03 can associate with other a/0 pairs. Studies in knockout mice implicate several subunits in the ability of nicotine to modulate dopamine neurons (a4, a6, a7, 02, 03) but... 

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