Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I.
The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 (5-HT3A) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with 5-HT3A receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current (I(5-HT)) with an IC50 of 64.7 +/- 2.2 microM. Inhibition was competitive and voltage-independent. Point mutations of pre-transmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the 5-HT3A receptor.
Lee
Byung-Hwan
BH
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Jeong
Sang-Min
SM
Jung
Sang-Min
SM
Lee
Jun-Ho
JH
Kim
Jong-Hoon
JH
Yoon
In-Soo
IS
Lee
Joon-Hee
JH
Choi
Sun-Hye
SH
Lee
Sang-Mok
SM
Chang
Choon-Gon
CG
Kim
Hyung-Chun
HC
Han
YeSun
Y
Paik
Hyun-Dong
HD
Kim
Yangmee
Y
Nah
Seung-Yeol
SY
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000187:drug effects* / Q000502:physiology; D011794:Quercetin / Q000378:metabolism / Q000494:pharmacology*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists; D014982:Xenopus laevis
D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D011794:Quercetin