Activation of transient receptor potential ankyrin 1 by quercetin and its analogs

Biosci Biotechnol Biochem. 2016 May;80(5):949-54. doi: 10.1080/09168451.2015.1132148. Epub 2016 Jan 25.

Abstract

The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1.

Keywords: TRPA1; flavonoid; metabolite; quercetin.

MeSH terms

  • Acetanilides / pharmacology
  • Aniline Compounds
  • Calcium / metabolism
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism
  • Dose-Response Relationship, Drug
  • Flavonoids / antagonists & inhibitors
  • Flavonoids / pharmacology*
  • Fluorescent Dyes
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Purines / pharmacology
  • Quercetin / antagonists & inhibitors
  • Quercetin / pharmacology*
  • Signal Transduction
  • Structure-Activity Relationship
  • TRPA1 Cation Channel
  • TRPV Cation Channels / genetics*
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels / agonists
  • Transient Receptor Potential Channels / genetics*
  • Transient Receptor Potential Channels / metabolism
  • Xanthenes

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Aniline Compounds
  • Calcium Channels
  • Flavonoids
  • Fluo 4
  • Fluorescent Dyes
  • Nerve Tissue Proteins
  • Purines
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels
  • Xanthenes
  • Quercetin
  • Calcium