Menthol inhibits 5-HT3 receptor-mediated currents

Abrar Ashoor, Jacob C. Nordman, Daniel Veltri, Keun Hang Susan Yang, Yaroslav Shuba, Lina Al Kury, Bassem Sadek, Frank C. Howarth, Amarda Shehu, Nadine Kabbani, Murat Oz

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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 [ 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-HT 3 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.

Original languageEnglish
Pages (from-to)398-409
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume347
Issue number2
DOIs
Publication statusPublished - Nov 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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