Elsevier

Progress in Neurobiology

Volume 53, Issue 2, October 1997, Pages 199-237
Progress in Neurobiology

Human neuronal nicotinic receptors

https://doi.org/10.1016/S0301-0082(97)00034-8Get rights and content

Abstract

Nicotine is a very widely used drug of abuse, which exerts a number of neurovegetative, behavioural and psychological effects by interacting with neuronal nicotinic acetylcholine receptors (NAChRs). These receptors are distributed widely in human brain and ganglia, and form a family of ACh-gated ion channels of different subtypes, each of which has a specific pharmacology and physiology. As human NAChRs have been implicated in a number of human central nervous system disorders (including the neurodegenerative Alzheimer's disease, schizophrenia and epilepsy), they are suitable potential targets for rational drug therapy.

Much of our current knowledge about the structure and function of NAChRs comes from studies carried out in other species, such as rodents and chicks, and information concerning human nicotinic receptors is still incomplete and scattered in the literature. Nevertheless, it is already evident that there are a number of differences in the anatomical distribution, physiology, pharmacology, and expression regulation of certain subtypes between the nicotinic systems of humans and other species.

This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining the molecular basis of their functional diversity viewed mainly from pharmacological and biochemical perspectives. It will also summarize our current knowledge concerning the structure and function of the NAChRs expressed by other species, and the newly discovered drugs used to classify their numerous subtypes. Finally, the role of NAChRs in behaviour and pathology will be considered.

References (298)

  • D.A. Brown et al.

    Dissociation of α-bungarotoxin binding and receptor block in the rat superior cervical ganglion

    Brain Res.

    (1977)
  • N.J. Cairns et al.

    [3H](−)nicotine binding sites in fetal human brain

    Brain Res.

    (1988)
  • J.M. Candy et al.

    Pathological changes in the nucleus of Meynert in Alzheimer's and Parkinson's diseases

    J. Neurol. Sci.

    (1983)
  • J.M. Candy et al.

    The current status of the cortical cholinergic system in Alzheimer's disease and Parkinson's disease

  • G.E. Cartier et al.

    A new α-conotoxin which targets εβ2 nicotinic acetylcholine receptors

    J. Biol. Chem.

    (1996)
  • B. Chini et al.

    Molecular cloning and chromosomal localization of the human α7-nicotinic receptor subunit gene

    Genomics

    (1994)
  • M. Cimino et al.

    Distribution of nicotinic receptors in cynomolgus monkey brain and ganglia: localization of α3 subunit mRNA, α-Bungarotoxin and nicotine binding sites

    Neuroscience

    (1992)
  • P.B. Clarke

    Nicotinic receptors in mammalian brain: localization and relation onto cholinergic functions

    Progr. Brain Res.

    (1993)
  • A. Codignola et al.

    Serotonin release and cell proliferation are under the control of α-bungarotoxin-sensitive nicotinic receptors in small-cell lung carcinoma cell lines

    FEBS Lett.

    (1994)
  • A. Codignola et al.

    α-Conotoxin Imperialis I inhibits nicotine-evoked hormone release and cell proliferation in human neuroendocrine carcinoma cells

    Neurosci. Lett.

    (1996)
  • W.G. Conroy et al.

    The α5 gene product assembles with multiple acetylcholine receptor subunits to form distinctive receptor subtypes in brain

    Neuron

    (1992)
  • W.G. Conroy et al.

    Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions

    J. Biol. Chem.

    (1995)
  • J. Court et al.

    The role of cholinergic system in the development of the human cerebellum

    Dev. Brain Res.

    (1995)
  • S. Couturier et al.

    A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomeric channel blocked by α-btx

    Neuron

    (1990)
  • J.A. Dani et al.

    Molecular and cellular aspects of nicotine abuse

    Neuron

    (1996)
  • L. Danober et al.

    Effects of cholinergic drugs on genetic absence seizures in rats

    Eur. J. Pharmacol.

    (1993)
  • P. Davies et al.

    Selective loss of central cholinergic neurons in Alzheimer's disease

    Lancet

    (1976)
  • M.W. Decker et al.

    Diversity of neuronal nicotinici acetylcholine receptors: lessons from behavior and implications for CNS therapeutics

    Life Sci.

    (1995)
  • D.L. Donnelly-Roberts et al.

    Functional modulation of human “ganglionic-like” neuronal nicotinic acetylcholine receptors (nAChRs) by l-type calcium channel antagonists

    Biochem. Biophys. Res. Comm.

    (1995)
  • S.M. Dursun et al.

    Long-lasting improvement of Tourette's syndrome with transdermal nicotine

    Lancet

    (1994)
  • A.B. Elgoyhen et al.

    α9: An acetylcholine receptor with novel pharmacological properties expressed in rat cochleae hair cells

    Cell

    (1994)
  • C.M. Eng et al.

    Mapping of multiple subunits of the neuronal nicotinic acetylcholine receptor to chromosome 15 in man and chromosome 9 in mouse

    Genomics

    (1991)
  • H.C. Fibiger

    The organization and some projections of cholinergic neurons of the mammalian forebrain

    Brain Res. Rev.

    (1982)
  • D. Fornasari et al.

    Molecular cloning of human neuronal nicotinic receptor α3-subunit

    Neurosci. Lett.

    (1990)
  • R. Freedman et al.

    Evidence in post-mortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia

    Biol. Psychiat.

    (1995)
  • J.-L. Galzi et al.

    Neuronal nicotinic receptors: molecular organization and regulations

    Neuropharmacology

    (1995)
  • M. Gopalakrishnan et al.

    Stable expression and pharmacological properties of the human α7 nicotinic acetylcholine receptor

    Eur. J. Pharmacol.

    (1995)
  • C. Gotti et al.

    Acetylcholine operated ion channel and α-bungarotoxin binding site in a human neuroblastoma cell line reside on different molecules

    Biochem. Biophys. Res. Comm.

    (1986)
  • C. Gotti et al.

    Cholinergic receptors, ion channels, neurotransmitter synthesis, and neurite outgrowth are independently regulated during the in vitro differentiation of a human neuroblastoma cell line

    Differentiation

    (1987)
  • C. Gotti et al.

    The α-bungarotoxin receptor purified from a human neuroblastoma cell line: biochemical and immunological characterization

    Neuroscience

    (1989)
  • A. Adem et al.

    Distribution of nicotinic receptors in human thalamus as visualized by 3H-nicotine and 3H-acetylcholine receptor autoradiography

    J. Neural Transm.

    (1988)
  • T. Akasu et al.

    5-Hydroxytryptamine decreases the sensitivity of nicotinic acetylcholine receptor in bull-frog sympathetic ganglion cells

    J. Physiol. (Load.)

    (1986)
  • E.X. Albuquerque et al.

    Nicotinic receptor function in the mammalian central nervous system

    Ann. NY Acad. Sci.

    (1995)
  • E.X. Albuquerque et al.

    Nicotinic acetylcholine receptors on hippocampal neurons: distribution on the neuronal surface and modulation of receptor activity

    J. Res. Rec.

    (1997)
  • M. Alkondon et al.

    Diversity of nicotinic acetylcholine receptors in rat brain. V. α-Bungarotoxin-sensitive nicotinic receptors in olfactory bulb neurons and presynaptic modulation of glutamate release

    J. Pharmacol. Expl Ther.

    (1996)
  • American Cancer Society

    Cancer Facts and Figures — 1994

  • R. Anand et al.

    Nucleotide sequence of the human nicotinic acetylcholine receptor β2 subunit gene

    Nucleic Acids Res.

    (1990)
  • R. Anand et al.

    Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes have a pentameric quaternary structure

    J. Biol. Chem.

    (1990)
  • R. Anand et al.

    Pharmacological characterization of α-bungarotoxin-sensitive acetylcholine receptors immunoisolated from chick retina: contrasting properties of α7 and α8 subunit-containing subtypes

    Mol. Pharmacol.

    (1993)
  • D.M. Araujo et al.

    Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease

    J. Neurochem.

    (1988)
  • Cited by (0)

    View full text