title: Inhibition of human α7 nicotinic acetylcholine receptors by cyclic monoterpene carveol.
abstract: 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 8.3µM. 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.
authors: Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors: Yosra
authors: Y
authors: Lozon
authors: Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors: Ahmed
authors: A
authors: Sultan
authors: Department of Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom.
authors: Stuart J
authors: SJ
authors: Lansdell
authors: Departments of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors: Tatiana
authors: T
authors: Prytkova
authors: Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors: Bassem
authors: B
authors: Sadek
authors: Departments of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors: Keun-Hang Susan
authors: KH
authors: Yang
authors: Department of Biological Sciences, Schmid College of Science and Technology, Chapman University, One University Drive, Orange, CA 92866, USA.
authors: Frank Christopher
authors: FC
authors: Howarth
authors: Department of Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom.
authors: Neil S
authors: NS
authors: Millar
authors: Laboratory of Functional Lipidomics, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Electronic address: Murat_Oz@uaeu.ac.ae.
authors: Murat
authors: M
authors: Oz
mesh_terms: D000818:Animals; D000081005:Cyclohexane Monoterpenes; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D006801:Humans; D062105:Molecular Docking Simulation; D039821:Monoterpenes / Q000378:metabolism / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D000072417:Protein Domains; D013997:Time Factors; D014982:Xenopus laevis / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D064569:alpha7 Nicotinic Acetylcholine Receptor; C075856:carveol
keywords: Carveol; Monoterpenes; Nicotinic acetylcholine receptor; Xenopus oocyte