Regulation By Nicotine Of Its Own Receptors

Department

neurobiology

Document Type

Article

Abstract

Nicotinic acetylcholine receptors (nAChR) are diverse members of the ligand-gated ion channel superfamily of neurotransmitter receptors and principal biological targets of nicotine action. Different nAChR subtypes play critical roles in chemical signaling throughout the brain and body and represent ideal targets for the modulation of nervous system function. Available evidence suggests that acute nicotine exposure activates function of all nAChR subtypes. However, more chronic exposure to nicotine, as would occur during long-term use of tobacco products, might have different effects on nAChR that could contribute to other changes in nervous system function. Our studies suggest that chronic nicotine exposure has some common effects on numbers and function of all nAChR subtypes examined. In model cell lines, numbers of muscle-type (α1β1γδ-nAChR), ganglionic (α3β4-nAChR), neuronal curaremimetic neurotoxin-binding (α7-nAChR), and central nervous system nicotine-binding (α4β2-nAChR) nicotinic receptors are increased on chronic exposure to nicotine. However, functional activity of muscle-type and ganglionic nAChR is lost through a process that is distinct from reversible desensitization of nAChR. Nevertheless, there is diversity in the magnitude, rate of onset, and nicotine dose dependence of these effects across nAChR subtypes. Moreover, the ability of other nicotinic ligands to mimic or block effects of chronic nicotine exposure differs across nAChR subtypes. These findings suggest that distinct nAChR subtypes, perhaps expressed in different quantities and/or sites of the nervous system across human individuals or animal strains, have unique sensitivities to chronic nicotine treatment, possibly helping to explain individual differences in responses to, and during recovery from, chronic nicotine exposure.

Publication Date

12-1-1996

Publication Title

Drug Development Research

ISSN

02724391

Volume

38

Issue

2019-03-04 00:00:00

First Page

136

Last Page

148

Digital Object Identifier (DOI)

10.1002/(SICI)1098-2299(199607/08)38:3/4<136::AID-DDR2>3.0.CO;2-N

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