Evodiamine functions as an agonist for the vanilloid receptor TRPV1

Larry V. Pearce, Pavel A. Petukhov, Tamas Szabo, Noemi Kedei, Fero Bizik, Alan P. Kozikowski, Peter M. Blumberg

Research output: Contribution to journalArticle

Abstract

Evodiamine, a quinozole alkaloid constituent of Evodia rutaecarpa, has been reported previously to induce several responses comparable to capsaicin in animal systems. Here, we characterize evodiamine as an agonist for rat TRPV1 expressed heterologously in CHO cells. Evodiamine bound to rat TRPV1 with a Ki of 5.95 ± 0.87 μM, as measured by inhibition of [ 3H] RTX binding (capsaicin, Ki= 1.8 ± 0.3 μM). Evodiamine was a full agonist for induction of 45Ca2+ uptake, with an EC50 of 856 ± 43 nM (capsaicin, EC 50 = 45 ± 4 nM) and was competitively antagonized by capsazepine, as revealed by a Schild plot. The pattern of cellular response, as determined by calcium imaging, was similar to that with capsaicin and yielded an EC50 of 1.03 ± 0.21 μM. Molecular modeling suggested a consistent pattern of overlap between evodiamine and TRPV1 agonists. We conclude that evodiamine represents a novel class of agonists for rat TRPV1, albeit 3-19-fold less potent than capsaicin, and thus represents a new potential class of lead molecules for drug development.

Original languageEnglish (US)
Pages (from-to)2281-2286
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume2
Issue number16
DOIs
StatePublished - Aug 21 2004

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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  • Cite this

    Pearce, L. V., Petukhov, P. A., Szabo, T., Kedei, N., Bizik, F., Kozikowski, A. P., & Blumberg, P. M. (2004). Evodiamine functions as an agonist for the vanilloid receptor TRPV1. Organic and Biomolecular Chemistry, 2(16), 2281-2286. https://doi.org/10.1039/b404506h