TY - JOUR
T1 - Inhibition of human α7 nicotinic acetylcholine receptors by cyclic monoterpene carveol
AU - Lozon, Yosra
AU - Sultan, Ahmed
AU - Lansdell, Stuart J.
AU - Prytkova, Tatiana
AU - Sadek, Bassem
AU - Yang, Keun Hang Susan
AU - Howarth, Frank Christopher
AU - Millar, Neil S.
AU - Oz, Murat
N1 - Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/4/5
Y1 - 2016/4/5
N2 - Cyclic monoterpenes are a group of phytochemicals with antinociceptive, local anesthetic, and anti-inflammatory actions. Effects of cyclic monoterpenes including vanilin, pulegone, eugenole, carvone, carvacrol, carveol, thymol, thymoquinone, menthone, and limonene were investigated on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes. Monoterpenes inhibited the α7 nicotinic acetylcholine receptor in the order carveol>thymoquinone>carvacrol>menthone>thymol>limonene>eugenole>pulegone≥carvone≥vanilin. Among the monoterpenes, carveol showed the highest potency on acetylcholine-induced responses, with IC50 of 8.3 μM. Carveol-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. In line with functional experiments, docking studies indicated that cyclic monoterpenes such as carveol may interact with an allosteric site located in the α7 transmembrane domain. Our results indicate that cyclic monoterpenes inhibit the function of human α7 nicotinic acetylcholine receptors, with varying potencies.
AB - Cyclic monoterpenes are a group of phytochemicals with antinociceptive, local anesthetic, and anti-inflammatory actions. Effects of cyclic monoterpenes including vanilin, pulegone, eugenole, carvone, carvacrol, carveol, thymol, thymoquinone, menthone, and limonene were investigated on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes. Monoterpenes inhibited the α7 nicotinic acetylcholine receptor in the order carveol>thymoquinone>carvacrol>menthone>thymol>limonene>eugenole>pulegone≥carvone≥vanilin. Among the monoterpenes, carveol showed the highest potency on acetylcholine-induced responses, with IC50 of 8.3 μM. Carveol-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. In line with functional experiments, docking studies indicated that cyclic monoterpenes such as carveol may interact with an allosteric site located in the α7 transmembrane domain. Our results indicate that cyclic monoterpenes inhibit the function of human α7 nicotinic acetylcholine receptors, with varying potencies.
KW - Carveol
KW - Monoterpenes
KW - Nicotinic acetylcholine receptor
KW - Xenopus oocyte
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UR - http://www.scopus.com/inward/citedby.url?scp=84960800028&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2016.02.004
DO - 10.1016/j.ejphar.2016.02.004
M3 - Article
C2 - 26849939
AN - SCOPUS:84960800028
SN - 0014-2999
VL - 776
SP - 44
EP - 51
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -