title: Quercetin enhances human α7 nicotinic acetylcholine receptor-mediated ion current through interactions with Ca(2+) binding sites.
abstract: The flavonoid quercetin is a low molecular weight substance found in fruits and vegetables. Aside from its anti-oxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions. The α7 nicotinic acetylcholine receptor (α7 nAChR) has a Ca(2+)-binding site, is highly permeable to the Ca(2+) ion, and plays important roles in Ca(2+)-related normal brain functions. Dysfunctions of α7 nAChR are associated with a variety of neurological disorders. In the present study, we investigated the effects of quercetin on the ACh-induced inward peak current (I(ACh)) in Xenopus oocytes that heterologously express human α7 nAChR. I(ACh) was measured with the two-electrode voltage clamp technique. In oocytes injected with α7 nAChR cRNA, the effects of the co-application of quercetin on I(ACh) were concentration-dependent and reversible. The ED(50) was 36.1 + 6.1 μM. Quercetin-mediated enhancement of I(ACh) caused more potentiation when quercetin was pre-applied. The degree of I(ACh) potentiation by quercetin pre-application was time-dependent and saturated after 1 min. Quercetin-mediated I(ACh) enhancement was not affected by ACh concentration and was voltage-independent. However, quercetin-mediated I(ACh) enhancement was dependent on extracellular Ca(2+) concentrations and was specific to the Ca(2+) ion, since the removal of extracellular Ca(2+) or the addition of Ba(2+) instead of Ca(2+) greatly diminished quercetin enhancement of I(ACh). The mutation of Glu195 to Gln195, in the Ca(2+)-binding site, almost completely diminished quercetin-mediated I(ACh) enhancement. These results indicate that quercetin-mediated I(ACh) enhancement human α7 nAChR heterologously expressed in Xenopus oocytes could be achieved through interactions with the Ca(2+)-binding site of the receptor.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Shin
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: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D017136:Ion Transport / Q000187:drug effects* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009865:Oocytes; D011794:Quercetin / Q000008:administration & dosage*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D011794:Quercetin; D002118:Calcium