Menthol Inhibits 5-Ht3 Receptor-Mediated Currents
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 mu M)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC50 = 163 mu M) manner. The effects of menthol developed gradually, reaching a steady-state level within 10-15 minutes and did not involve G-proteins, since GTP gamma S 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 [H-3]GR65630 was not altered in the presence of menthol (up to 1 mu M), 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 mu M). These data demonstrate that menthol, at pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT3 receptors.
Ashoor, Abrar, Jacob C. Nordman, Daniel Veltri, Keun-Hang Susan Yang, Yaroslav Shuba, Lina Al Kury, Bassem Sadek et al. Menthol Inhibits 5-HT3 Receptor–Mediated Currents. Journal of Pharmacology and Experimental Therapeutics 2013; 347(2): 398-409.
American Society for Pharmacology and Experimental Therapeutics