title: Menthol inhibits 5-HT3 receptor-mediated currents.
abstract: The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT3) receptors expressed in Xenopus laevis oocytes. 5-HT (1 μM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC50 = 163 μM) manner. The effects of menthol developed gradually, reaching a steady-state level within 10-15 minutes and did not involve G-proteins, since GTPγS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (-), (+), and racemic menthol inhibited 5-HT3 receptor-mediated currents to the same extent. Menthol inhibition was not altered by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by increasing concentrations of 5-HT. Furthermore, specific binding of the 5-HT3 antagonist [(3)H]GR65630 was not altered in the presence of menthol (up to 1 mM), indicating that menthol acts as a noncompetitive antagonist of the 5-HT3 receptor. Finally, 5-HT3 receptor-mediated currents in acutely dissociated nodose ganglion neurons were also inhibited by menthol (100 μM). These data demonstrate that menthol, at pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT3 receptors.
authors: Laboratory of Functional Lipidomics, Departments of Pharmacology (A.A., L.A.K., B.S., M.O.) and Physiology (F.C.H.), College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates; Department of Molecular Neuroscience (J.C.N., N.K.), School of Systems Biology (D.V.), and Department of Computer Science (A.S.), George Mason University, Fairfax, Virginia; International Center of Molecular Physiology of the National Academy of Sciences of Ukraine, Kiev, Ukraine (Y.S.); and Department of Biological Sciences, Schmid College of Science and Engineering, Chapman University, Orange, California (K.-H.S.Y.).
authors: Abrar
authors: A
authors: Ashoor
authors: Jacob C
authors: JC
authors: Nordman
authors: Daniel
authors: D
authors: Veltri
authors: Keun-Hang Susan
authors: KH
authors: Yang
authors: Yaroslav
authors: Y
authors: Shuba
authors: Lina
authors: L
authors: Al Kury
authors: Bassem
authors: B
authors: Sadek
authors: Frank C
authors: FC
authors: Howarth
authors: Amarda
authors: A
authors: Shehu
authors: Nadine
authors: N
authors: Kabbani
authors: Murat
authors: M
authors: Oz
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008610:Menthol / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D007093:Imidazoles; D007211:Indoles; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C059068:GR 65630; D008610:Menthol