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

Mol Cells. 2005 Aug 31;20(1):69-73.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Oocytes / physiology
  • Protein Structure, Tertiary / drug effects*
  • Protein Structure, Tertiary / physiology
  • Quercetin / metabolism
  • Quercetin / pharmacology*
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Serotonin 5-HT3 Receptor Antagonists*
  • Xenopus laevis


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