title: Effects of quercetin on human α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated ion currents.
abstract: Quercetin is a low molecular weight flavonoid found in dietary fruits and vegetables. Quercetin, like other flavonoids, has demonstrated neuroprotective effects in vitro and in vivo. However, relatively little is known about how quercetin achieves its neuroprotective abilities. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is one of several excitatory receptors, which play an important role in postsynaptic neurotransmission. Over-stimulation of ionotropic glutamate receptor including AMPA receptors is closely associated with excitatory neurotoxicities. In the present study, we investigated the effects of quercetin on the glutamate-induced inward current (IGlu) in Xenopus oocytes that heterologously express human AMPA receptor and stargazin, an auxiliary subunit of AMPA receptor. IGlu was measured using the two-electrode voltage clamp technique. In oocytes injected with cRNAs coding AMPA receptor (GluR1) and stargazin, quercetin inhibited IGlu in a reversible and concentration-dependent manner. The IC50 was 84.9+/-15.0 microM. Quercetin action on IGlu was attenuated by increasing glutamate concentration, and was membrane holding potential-dependent. These results show a possibility that quercetin interacts with AMPA receptor, which was heterologously expressed in Xenopus oocytes and that quercetin action on IGlu of AMPA receptor could be one of contributions of quercetin-mediated neuroprotections.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Shin
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Pyo
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Kim
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Lee
authors.forename: Ye Sun
authors.initials: YS
authors.lastname: Han
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology*; D011794:Quercetin / Q000378:metabolism / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000378:metabolism* / Q000502:physiology; D014982:Xenopus laevis
chemical_list: C491912:CACNG2 protein, human; D015220:Calcium Channels; D018091:Receptors, AMPA; D011794:Quercetin