Effects of quercetin on human α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated ion currents.
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.
Shin
Tae-Joon
TJ
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
Choi
Sun-Hye
SH
Lee
Byung-Hwan
BH
Pyo
Mi Kyung
MK
Hwang
Sung-Hee
SH
Kim
Bo-Ra
BR
Lee
Sang-Mok
SM
Han
Ye Sun
YS
Lee
Jun-Ho
JH
Park
Ji-Ho
JH
Kim
Hyoung-Chun
HC
Rhim
Hyewhon
H
Nah
Seung-Yeol
SY
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
C491912:CACNG2 protein, human; D015220:Calcium Channels; D018091:Receptors, AMPA; D011794:Quercetin