Presynaptic nicotinic acetylcholine receptors in the brain

S Wonnacott, L Soliakov, G Wilkie, P Redfern, D Marshall

Research output: Contribution to journalArticle

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Abstract

Nicotine, acting through nicotinic acetylcholine receptors (nAChR) located on nerve terminals, can evoke the release of various neurotransmitters in the brain. The presynaptic nicotinic stimulation of acetylcholine release, demonstrated in cortical and hippocampal preparations, may reflect a positive feedback mechanism via autoreceptors. This site is a target for novel nicotinic agonists in the symptomatic treatment of Alzheimer's disease. Nicotinic heteroreceptors can modulate the release of catecholamines and amino acid transmitters in diverse brain regions. Differences in agonist potency and efficacy and in antagonist sensitivities between different transmitter pathways suggests heterogeneity of subtypes of presynaptic nAChR (notably between alpha 3- and alpha 4-containing nAChR). While neurochemical studies have failed to find any evidence for the involvement of alpha 7-type nAChR in the presynaptic modulation of transmitter release, recent electrophysiological studies have disclosed this as a possibility with respect to glutamate transmission. Investigation of the mechanisms coupling nAChR activation to exocytosis suggests that despite their high relative permeability to Ca2+, nAChR on striatal terminals promote dopamine release by opening voltage-sensitive Ca2+ channels, principally N-type channels. Comparison of in vitro preparations with in vivo studies confirms that nicotine (administered via a microdialysis probe) can elicit dopamine release from the terminal fields of the three major dopamine pathways: This is dose dependent and mecamylamine sensitive. However, release from striatum and accumbens (but not frontal cortex) is completely blocked by tetrodotoxin, compared with a partial block (40%) of release from synaptosomes. In vivo, nicotine may be able to influence dopamine release by acting on 1) ''pre-terminal'' nAChR, 2) presynaptic nAChR on adjacent glutamatergic terminals, or 3) local interneurones bearing nAChR, in addition to a direct action th rough presynaptic nAChR on dopaminergic terminals. Thus, a complex picture is emerging of various loci at which nicotine and other agonists can act through a variety of nAChR subtypes to influence neurotransmitter release: The significance of this phenomenon for synaptic transmission is discussed.
LanguageEnglish
Pages149-159
Number of pages11
JournalDrug Development Research
Volume38
Issue number3-4
DOIs
StatusPublished - Jul 1996

Fingerprint

Nicotinic Receptors
Brain
Nicotine
Dopamine
Neurotransmitter Agents
Nicotinic Agonists
Mecamylamine
Corpus Striatum
Autoreceptors
Synaptosomes
Microdialysis
Exocytosis
Tetrodotoxin
Frontal Lobe
Interneurons
Synaptic Transmission
Acetylcholine
Catecholamines
Glutamic Acid
Permeability

Keywords

  • cerebral cortical synaptosomes
  • nicotinic ach reception
  • extracellular levels
  • modulation
  • nucleus-accumbens
  • transmitter release
  • dopamine release
  • rat striatal synaptosomes
  • systemic nicotine
  • stimulation
  • h-3 dopamine release
  • pharmacological characterization
  • brain

Cite this

Presynaptic nicotinic acetylcholine receptors in the brain. / Wonnacott, S; Soliakov, L; Wilkie, G; Redfern, P; Marshall, D.

In: Drug Development Research, Vol. 38, No. 3-4, 07.1996, p. 149-159.

Research output: Contribution to journalArticle

Wonnacott, S ; Soliakov, L ; Wilkie, G ; Redfern, P ; Marshall, D. / Presynaptic nicotinic acetylcholine receptors in the brain. In: Drug Development Research. 1996 ; Vol. 38, No. 3-4. pp. 149-159
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