Differential regulations of quercetin and its glycosides on ligand-gated ion channels.
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-(2G-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-HT3A receptor channel activities are not well known. In the present study, we investigated the effects of quercetin glycosides on the human glycine alpha1 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> or =Rham1>Rham2. Applications of quercetin and its glycosides inhibited I5-HT in order of Rham2> or =quercetin>Rutin=Rham1. The inhibitions of IGly by quercetin glycosides were non-competitive and voltage-sensitive, whereas the inhibitions of I5-HT by quercetin glycosides were competitive and voltage-insensitive manners. These results also indicate that quercetin glycosides might regulate the human glycine alpha1 and mouse 5-HT3A receptors with differential manners.
Lee
Byung-Hwan
BH
Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
Pyo
Mi Kyung
MK
Lee
Jun-Ho
JH
Choi
Sun-Hye
SH
Shin
Tae-Joon
TJ
Lee
Sang-Mok
SM
Lim
Yoongho
Y
Han
Ye Sun
YS
Paik
Hyun-Dong
HD
Cho
Ssang-Goo
SG
Yun-Choi
Hye Sook
HS
Rhim
Hyewhon
H
Nah
Seung-Yeol
SY
D000818:Animals; D004594:Electrophysiology; D006027:Glycosides / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008845:Microinjections; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011794:Quercetin / Q000494:pharmacology*; D018075:RNA, Complementary / Q000096:biosynthesis; D018009:Receptors, Glycine / Q000187:drug effects / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D012431:Rutin / Q000494:pharmacology; D014981:Xenopus
D006027:Glycosides; D007473:Ion Channels; D008024:Ligands; D018075:RNA, Complementary; D018009:Receptors, Glycine; D044406:Receptors, Serotonin, 5-HT3; D012431:Rutin; D011794:Quercetin