Menthol inhibits 5-HT3 receptor-mediated currents.
نویسندگان
چکیده
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 [(3)H]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.
منابع مشابه
Jpet #203976 Menthol Inhibits 5-ht3 Receptor-mediated Currents
The effects of alcohol monoterpene menthol, a major active ingredient of the 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 concentrationdependent (IC50=163 μM) manner. The effects of menthol develo...
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ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 347 2 شماره
صفحات -
تاریخ انتشار 2013