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Effects of Menthol on α3β4∗ Nicotinic Receptors

Patowary, Suparna and Mackey, Elisha D. W. and McKinney, Sheri L. and Deshpande, Purnima and Henderson, Brandon J. and Biener, Gabriel and Raicu, Valerica and Lester, Henry A. (2016) Effects of Menthol on α3β4∗ Nicotinic Receptors. Biophysical Journal, 110 (3). 603A. ISSN 0006-3495. doi:10.1016/j.bpj.2015.11.3221.

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Manufacturers add menthol to roughly 30% of tobacco cigarettes sold in the US, and to an unknown fraction of other tobacco products and electronic cigarettes. Smokers of menthol cigarettes find it harder to quit smoking, raising questions about the mechanism of this apparently harmful menthol effect. Menthol modestly affects the pharmacokinetics of nicotine and acts as a chemical chaperone for nicotinic acetylcholine receptors (nAChRs) [1]. In this study, we have investigated the effects of menthol on α3β4∗ nAChRs, which are mostly expressed in medial habenula (MHb) - interpeduncular nucleus (IPN) circuit: a key mediator of nicotine's aversive properties and withdrawal [2]. Fluorescently labeled α3 and β4 subunits are transiently expressed in Neuro-2a cells to form monomers, and oligomers. Using a Förster Resonance Energy Transfer (FRET) micro-spectroscopy method [3], we have found that menthol up-regulates α3 subunit while having no effects on β4 subunit and α3β4 pentamer numbers. Our results also show that menthol favors (α3)3(β4)2 stoichiometry over (α3)2(β4)3 stoichiometry. However, the study using Total Internal Reflection Fluorescence Microscopy (TIRFM) reveals that though menthol up-regulates α3 subunit numbers in peripheral Endoplasmic Reticulum, it decreases the α3β4 receptor numbers at the plasma membrane.

Item Type:Article
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Henderson, Brandon J.0000-0003-0381-028X
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2016 Biophysical Society. Published by Elsevier Inc.
Issue or Number:3
Record Number:CaltechAUTHORS:20160606-140410523
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Official Citation:Suparna Patowary, Elisha D.W. Mackey, Sheri L. McKinney, Purnima Deshpande, Brandon J. Henderson, Gabriel Biener, Valerica Raicu, Henry A. Lester, Effects of Menthol on α3β4∗ Nicotinic Receptors, Biophysical Journal, Volume 110, Issue 3, Supplement 1, 16 February 2016, Page 603a, ISSN 0006-3495, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67695
Deposited By: Tony Diaz
Deposited On:06 Jun 2016 21:08
Last Modified:11 Nov 2021 03:53

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