title: Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation.
abstract: In this study, we have investigated how the function of native and recombinant nicotinic acetylcholine receptors (nAChRs) is modulated by the monoterpenoid alcohol from peppermint (-) menthol. In trigeminal neurons (TG), we found that nicotine (75 μM)-activated whole-cell currents through nAChRs were reversibly reduced by menthol in a concentration-dependent manner with an IC₅₀ of 111 μM. To analyze the mechanism underlying menthol's action in more detail, we used single channel and whole-cell recordings from recombinant human α4β2 nAChR expressed in HEK tsA201 cells. Here, we found a shortening of channel open time and a prolongation of channel closed time, and an increase in single channel amplitude leading in summary to a reduction in single channel current. Furthermore, menthol did not affect nicotine's EC₅₀ value for currents through recombinant human α4β2 nAChRs but caused a significant reduction in nicotine's efficacy. Taken together, these findings indicate that menthol is a negative allosteric modulator of nAChRs.
authors.affiliation: Department of Physiology, University of Bonn, Nussallee 11, D-53115 Bonn, Germany. michael.hans@ukb.uni-bonn.de
authors.forename: M
authors.initials: M
authors.lastname: Hans
authors.forename: M
authors.initials: M
authors.lastname: Wilhelm
authors.forename: D
authors.initials: D
authors.lastname: Swandulla
mesh_terms: D000200:Action Potentials; D000494:Allosteric Regulation; D000818:Animals; D002460:Cell Line; D006801:Humans; D036142:Mentha piperita / Q000737:chemistry; D008610:Menthol / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D014162:Transfection; D014276:Trigeminal Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D008610:Menthol; D009538:Nicotine