Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I.

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-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.

• Authors: Byung-Hwan Lee, Sang-Min Jeong, Sang-Min Jung, Jun-Ho Lee, Jong-Hoon Kim, In-Soo Yoon, Joon-Hee Lee, Sun-Hye Choi, Sang-Mok Lee, Choon-Gon Chang, Hyung-Chun Kim, YeSun Han, Hyun-Dong Paik, Yangmee Kim, Seung-Yeol Nah
• Journal: Molecules and cells (Mol Cells) Vol. 20 Issue 1 Pg. 69-73 (Aug 31 2005) ISSN: 1016-8478 [Print] United States
• PMID: 16258243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Serotonin, 5-HT3
• Serotonin 5-HT3 Receptor Antagonists
• Quercetin

Topics

• Animals
• Dose-Response Relationship, Drug
• Female
• Ion Channel Gating (drug effects)
• Ion Transport (drug effects)
• Membrane Potentials (drug effects)
• Mice
• Mutagenesis, Site-Directed
• Oocytes (metabolism, physiology)
• Protein Structure, Tertiary (drug effects, physiology)
• Quercetin (metabolism, pharmacology)
• Receptors, Serotonin, 5-HT3 (metabolism)
• Serotonin 5-HT3 Receptor Antagonists
• Xenopus laevis