RT Journal Article
SR Electronic
T1 MENTHOL INHIBITS 5-HT3 RECEPTOR-MEDIATED CURRENTS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.113.203976
DO 10.1124/jpet.113.203976
A1 Abrar Ashoor
A1 Jacob Nordman
A1 Daniel Veltri
A1 Keun-Hang Susan Yang
A1 Yaroslav Shuba
A1 Lina Al Kury
A1 Bassem Sadek
A1 Frank Christopher Howarth
A1 Amarda Shehu
A1 Nadine Kabbani
A1 Murat Oz
YR 2013
UL http://jpet.aspetjournals.org/content/early/2013/08/21/jpet.113.203976.abstract
AB The effects of alcohol monoterpene menthol, a major active ingredient of peppermint plant was tested on the function of human hydroxytryptamine type 3 (5-HT3) receptors expressed in Xenopus 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 min, and did not involve G-proteins, since GTP-γ-S activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereo-selective since (-), (+), and racemic menthol inhibited 5-HT3 receptor mediated currents to the same extent. Menthol inhibition was not altered by intracellular BAPTA injections and trans-membrane potential changes. The maximum inhibition observed for menthol was not reversed by increasing concentrations of 5-HT. Furthermore, specific binding of 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 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.