Differential regulations of quercetin and its glycosides on ligand-gated ion channels

Abstract

Quercetin, one of the flavonoids, is a compound of low molecular weight found in various plants and shows a wide range of diverse neuropharmacological actions. In fruits and vegetables, quercetin exists as monomer-(quercetin-3-O- rhamnoside) (Rham1), dimer- (Rutin), or trimer-glycosides [quercetin-3-(2 G-rhamnosylrutinoside)] (Rham2) at carbon-3. In the previous studies, we demonstrated that quercetin inhibits both glycine and 5-hydroxytryptamine type 3, (5-HT3A) receptor channel activities expressed in Xenopus oocytes. However, the effects of quercetin glycosides on glycine and 5-HT 3A receptor channel activities are not well known. In the present study, we investigated the effects of quercetin glycosides on the human glycine α1 receptor and mouse 5-HT3A receptor channel activities expressed in Xenopus oocytes using a two-electrode voltage clamp technique. In oocytes expressing glycine or 5-HT3A receptors, quercetin- or its glycosides-induced inhibitions on glycine- (IGly) and 5-HT-induced current (I5-HT) were dose-dependent and reversible. Applications of quercetin and its glycosides inhibited IGly in order of quercetin>Rutin≥Rham1>Rham2. Applications of quercetin and its glycosides inhibited I5-HT in order of Rham2≥quercetin>Rutin= Rham1. The inhibitions of IGly by quercetin glycosides were non-competitive and voltage-sensitive, whereas the inhibitions of I 5-HT by quercetin glycosides were competitive and voltage-insensitive manners. These results also indicate that quercetin glycosides might regulate the human glycine α1 and mouse 5-HT3A receptors with differential manners. © 2008 Pharmaceutical Society of Japan.