Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
15 05 2020
15 05 2020
Historique:
received:
24
12
2019
revised:
05
02
2020
accepted:
25
02
2020
pubmed:
9
3
2020
medline:
28
5
2021
entrez:
9
3
2020
Statut:
ppublish
Résumé
Postsynaptic nAChRs in the peripheral nervous system are critical for neuromuscular and autonomic neurotransmission. Pre- and peri-synaptic nAChRs in the brain modulate neurotransmission and are responsible for the addictive effects of nicotine. Subtypes of nAChRs in lymphocytes and non-synaptic locations may modulate inflammation and other cellular functions. All AChRs that function as ligand-gated ion channels are formed from five homologous subunits organized to form a central cation channel whose opening is regulated by ACh bound at extracellular subunit interfaces. nAChR subtype subunit composition can range from α7 homomers to α4β2α6β2β3 heteromers. Subtypes differ in affinities for ACh and other agonists like nicotine and in efficiencies with which their channels are opened and desensitized. Subtypes also differ in affinities for antagonists and for positive and negative allosteric modulators. Some agonists are "silent" with respect to channel opening, and AChRs may be able to signal metabotropic pathways by releasing G-proteins independent of channel opening. Electrophysiological studies that can resolve single-channel openings and molecular genetic approaches have allowed characterization of the structures of ligand binding sites, the cation channel, and the linkages between them, as well as the organization of AChR subunits and their contributions to function. Crystallography and cryo-electron-microscopy are providing increasing insights into the structures and functions of AChRs. However, much remains to be learned about both AChR structure and function, the in vivo functional roles of some AChR subtypes, and the development of better pharmacological tools directed at AChRs to treat addiction, pain, inflammation, and other medically important issues. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.
Identifiants
pubmed: 32146229
pii: S0028-3908(20)30087-3
doi: 10.1016/j.neuropharm.2020.108021
pmc: PMC7610230
mid: NIHMS1575534
pii:
doi:
Substances chimiques
Ligands
0
Nicotinic Agonists
0
Nicotinic Antagonists
0
Receptors, Nicotinic
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108021Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM057481
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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