PT  - JOURNAL ARTICLE
AU  - Ashoor, Abrar
AU  - Nordman, Jacob C.
AU  - Veltri, Daniel
AU  - Yang, Keun-Hang Susan
AU  - Shuba, Yaroslav
AU  - Al Kury, Lina
AU  - Sadek, Bassem
AU  - Howarth, Frank C.
AU  - Shehu, Amarda
AU  - Kabbani, Nadine
AU  - Oz, Murat
TI  - Menthol Inhibits 5-HT<sub>3</sub> Receptor–Mediated Currents
AID  - 10.1124/jpet.113.203976
DP  - 2013 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 398--409
VI  - 347
IP  - 2
4099  - http://jpet.aspetjournals.org/content/347/2/398.short
4100  - http://jpet.aspetjournals.org/content/347/2/398.full
SO  - J Pharmacol Exp Ther2013 Nov 01; 347
AB  - 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 [3H]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.