title: Differential effects of quercetin glycosides on GABAC receptor channel activity.
abstract: Quercetin, a representative flavonoid, is a compound of low molecular weight found in various colored plants and vegetables. Quercetin shows a wide range of neuropharmacological activities. In fact, quercetin naturally exists as monomer-(quercetin-3-O-rhamnoside) (Rham1), dimer-(Rutin), or trimer-glycosides [quercetin-3-(2(G)-rhamnosylrutinoside)] (Rham2) at carbon-3 in fruits and vegetables. The carbohydrate components are removed after ingestion into gastrointestinal systems. The role of the glycosides attached to quercetin in the regulation of γ-aminobutyric acid class C (GABAC) receptor channel activity has not been determined. In the present study, we examined the effects of quercetin glycosides on GABAC receptor channel activity by expressing human GABAC alone in Xenopus oocytes using a two-electrode voltage clamp technique and also compared the effects of quercetin glycosides with quercetin. We found that GABA-induced inward current (I GABA ) was inhibited by quercetin or quercetin glycosides. The inhibitory effects of quercetin and its glycosides on I GABA were concentration-dependent and reversible in the order of Rutin ≈ quercetin ≈ Rham 1 > Rham 2. The inhibitory effects of quercetin and its glycosides on I GABA were noncompetitive and membrane voltage-insensitive. These results indicate that quercetin and its glycosides regulate GABAC receptor channel activity through interaction with a different site from that of GABA, and that the number of carbohydrate attached to quercetin might play an important role in the regulation of GABAC receptor channel activity.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul, 143-701, Korea.
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Seok-Won
authors.initials: SW
authors.lastname: Jung
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Joon-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Pyo
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018079:Receptors, GABA / Q000502:physiology*; D012431:Rutin / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D018756:GABA Antagonists; C087200:GABA-C receptor; D006027:Glycosides; D018079:Receptors, GABA; C012526:quercitrin; D012431:Rutin; D011794:Quercetin