Research

Presynaptic nicotinic acetylcholine receptors in the brain


Reference:

Wonnacott, S., Soliakov, L., Wilkie, G., Redfern, P. and Marshall, D., 1996. Presynaptic nicotinic acetylcholine receptors in the brain. Drug Development Research, 38 (3-4), pp. 149-159.

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Official URL:

http://dx.doi.org/10.1002/(SICI)1098-2299(199607/08)38:3/4<149::AID-DDR3>3.0.CO;2-M

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.

Details

Item Type Articles
CreatorsWonnacott, S., Soliakov, L., Wilkie, G., Redfern, P. and Marshall, D.
DOI10.1002/(SICI)1098-2299(199607/08)38:3/4<149::AID-DDR3>3.0.CO;2-M
Uncontrolled Keywordscerebral 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
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code4447
Additional InformationID number: ISI:A1996WA75400003

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