Menthol binding and inhibition of α7-nicotinic acetylcholine receptors

Abrar Ashoor; Jacob C Nordman; Daniel Veltri; Keun-Hang Susan Yang; Lina Al Kury; Yaroslav Shuba; Mohamed Mahgoub; Frank C Howarth; Bassem Sadek; Amarda Shehu; Nadine Kabbani; Murat Oz

doi:10.1371/journal.pone.0067674

Menthol binding and inhibition of α7-nicotinic acetylcholine receptors

PLoS One. 2013 Jul 23;8(7):e67674. doi: 10.1371/journal.pone.0067674. Print 2013.

Authors

Abrar Ashoor¹, Jacob C Nordman, Daniel Veltri, Keun-Hang Susan Yang, Lina Al Kury, Yaroslav Shuba, Mohamed Mahgoub, Frank C Howarth, Bassem Sadek, Amarda Shehu, Nadine Kabbani, Murat Oz

Affiliation

¹ Department of Pharmacology Laboratory of Functional Lipidomics, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.

Abstract

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+)-dependent Cl(-) channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing Ba(2+). Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125)I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+) transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acetylcholine / pharmacology
Amino Acid Sequence
Animals
Binding Sites
Bungarotoxins / metabolism
Calcium Signaling / drug effects
Female
Humans
Ion Channel Gating / drug effects
Membrane Potentials / drug effects
Menthol / metabolism*
Menthol / pharmacology
Molecular Sequence Data
Neurons / drug effects
Neurons / metabolism
Neurotransmitter Agents / metabolism
Oocytes / drug effects
Oocytes / metabolism
PC12 Cells
Rats
Sequence Alignment
Time Factors
Xenopus laevis
alpha7 Nicotinic Acetylcholine Receptor / antagonists & inhibitors
alpha7 Nicotinic Acetylcholine Receptor / chemistry
alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

Bungarotoxins
Neurotransmitter Agents
alpha7 Nicotinic Acetylcholine Receptor
Menthol
Acetylcholine

Grants and funding

This study was supported by grants from CMHS, UAE University and support from IRP/NIDA of NIH, DHHS to MO and a Jeffress Memorial Trust Grant (J-953) to NK. DV is supported in part by NSF IIS CAREER Award No. 1144106 to AS. Research in our laboratory is also supported by LABCO partner of Sigma-Aldrich. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.