Presynaptic Nicotinic Receptors and the Modulation of Transmitter Release

  1. Greg Bock Organizer and
  2. Joan Marsh
  1. Susan Wonnacott1,
  2. Alison Drasdo1,
  3. Elizabeth Sanderson1 and
  4. Peter Rowell2

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513965.ch6

Ciba Foundation Symposium 152 - The Biology of Nicotine Dependence

Ciba Foundation Symposium 152 - The Biology of Nicotine Dependence

How to Cite

Wonnacott, S., Drasdo, A., Sanderson, E. and Rowell, P. (2007) Presynaptic Nicotinic Receptors and the Modulation of Transmitter Release, in Ciba Foundation Symposium 152 - The Biology of Nicotine Dependence (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513965.ch6

Author Information

  1. 1

    Biochemistry Department, University of Bath, Claverton Down, Bath BA2 7AY, UK

  2. 2

    Department of Pharmacology and Toxicology, University of Louisville, Kentucky, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471926887

Online ISBN: 9780470513965

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Keywords:

  • presynaptic nicotinic receptors;
  • transmitter release;
  • nicotinic receptors;
  • chronic administration;
  • sensitivity

Summary

Nicotine is increasingly recognized to promote transmitter release in the brain by a direct action on presynaptic terminals. Pharmacological evidence indicates that this action is mediated by nicotinic receptors. From their sensitivity to mecamylamine, neosurugatoxin and neuronal bungarotoxin these presynaptic receptors can be distinguished from α-bungarotoxin-sensitive muscle-type nicotinic receptors, and can be correlated with [3H]nicotine binding sites in the brain. The release of many transmitters in different brain regions is susceptible to stimulation by nicotine, but this effect is not ubiquitous. However, lesioning and subcellular fractionation studies suggest that the majority of brain nicotinic receptors are located presynaptically, so that a direct influence of nicotine on transmitter release assumes considerable importance. Although the sensitivity of presynaptic receptors is such that they are likely to be partially activated by doses of nicotine obtained by smoking, the desensitization-induced up-regulation of nicotinic binding sites that follows chronic nicotine treatment raises questions about their functional status during tobacco usage. Chronic administration of the agonist (+)anatoxin-a also up-regulated [3H] nicotine binding sites, and led to increased nicotine-evoked transmitter release in vitro. This could have implications for the involvement of these receptors during withdrawal.