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Quercetin Inhibits the 5-Hydroxytryptamine Type 3 Receptor-mediated Ion Current by Interacting with Pre-Transmembrane Domain I  

Lee, Byung-Hwan (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Jung, Sang-Min (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Lee, Jun-Ho (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Kim, Jong-Hoon (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Yoon, In-Soo (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Lee, Joon-Hee (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Choi, Sun-Hye (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Lee, Sang-Mok (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Chang, Choon-Gon (Department of Pharmacology, College of Pharmacy, Sungkyunkwan University)
Kim, Hyung-Chun (College of Pharmacy, Kangwon National University)
Han, YeSun (Department of Advanced Technology Fusion and Bio/Molecular Informatics Center, Konkuk University)
Paik, Hyun-Dong (Division of Animal Life Science and Bio/Molecular Informatics Center, Konkuk University)
Kim, Yangmee (Department of Chemistry and Bio/Molecular Informatics Center, Konkuk University)
Nah, Seung-Yeol (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
Publication Information
Molecules and Cells / v.20, no.1, 2005 , pp. 69-73 More about this Journal
Abstract
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 ($5-HT_{3A}$) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The $5-HT_{3A}$ receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with $5-HT_{3A}$ receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current ($I_{5-HT}$) with an $IC_{50}$ of $64.7{\pm}2.2{\mu}M$. 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 $5-HT_{3A}$ receptor.
Keywords
$5-HT_{3A}$ Receptor; Flavonoids; Ligand-gated Ion Channels; Quercetin; Serotonin; Site-directed Mutagenesis; Xenopus Oocytes;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 20  (Related Records In Web of Science)
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