Nicotinic acetylcholine receptor stimulation impairs epidermal permeability barrier function and recovery and modulates cornified envelope proteins.

Journal Article (Journal Article)

AIM: To characterize how nicotinic acetylcholine receptors (nAChRs) influence epidermal barrier function and recovery following prolonged stress or direct nAChR activation or antagonism. MAIN METHODS: Mice were subjected to psychological stress or treated topically with nAChR agonist or antagonist for 3 days. We assessed barrier permeability and recovery by measuring transepidermal water loss (TEWL) before and after barrier disruption. In parallel, we analyzed the production and localization of several epidermal cornified envelope proteins in mouse skin and in human EpiDerm™ organotypic constructs stimulated with a nAChR agonist (nicotine) and/or a nAChR selective antagonist (α-bungarotoxin). KEY FINDINGS: We determined that psychological stress in mice impairs barrier permeability function and recovery, an effect that is reversed by application of the α7 selective nAChR antagonist, α-bungarotoxin (Bung). In the absence of stress, both topical nicotine or Bung treatment alone impaired barrier permeability. We further observed that stress, topical nicotine, or topical Bung treatment in mice influenced the abundance and/or localization of filaggrin, loricrin, and involucrin. Similar alterations in these three major cornified envelope proteins were observed in human EpiDerm™ cultures. SIGNIFICANCE: Perceived psychological stress and nicotine usage can both initiate or exacerbate several dermatoses by altering the cutaneous permeability barrier. Modulation of nAChRs by topical agonists or antagonists may be used to improve epidermal barrier function in skin diseases associated with defects in epidermal barrier permeability.

Full Text

Duke Authors

Cited Authors

  • Curtis, BJ; Plichta, JK; Blatt, H; Droho, S; Griffin, TM; Radek, KA

Published Date

  • November 27, 2012

Published In

Volume / Issue

  • 91 / 21-22

Start / End Page

  • 1070 - 1076

PubMed ID

  • 22940618

Pubmed Central ID

  • PMC3549432

Electronic International Standard Serial Number (EISSN)

  • 1879-0631

Digital Object Identifier (DOI)

  • 10.1016/j.lfs.2012.08.020


  • eng

Conference Location

  • Netherlands