Issue 16, 2004
From the journal:

Organic & Biomolecular Chemistry

Evodiamine functions as an agonist for the vanilloid receptor TRPV1

Larry V. Pearce,a   Pavel A. Petukhov,b   Tamas Szabo,a   Noemi Kedei,a   Fero Bizik,b   Alan P. Kozikowskib  and  Peter M. Blumberg*a  

* Corresponding authors

a Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, USA
E-mail: blumberp@dc37a.nci.nih.gov
Fax: 301-496-8709
Tel: 301-496-3189

b Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, IL, USA

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, EC50 = 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.

Graphical abstract: Evodiamine functions as an agonist for the vanilloid receptor TRPV1

About
Cited by
Related
Download options Please wait...

Article information

DOI
https://doi.org/10.1039/B404506H
Article type
Paper
Submitted
26 Mar 2004
Accepted
29 Jun 2004
First published
27 Jul 2004

Org. Biomol. Chem., 2004,2, 2281-2286

Permissions

Request permissions

Evodiamine functions as an agonist for the vanilloid receptor TRPV1

L. V. Pearce, P. A. Petukhov, T. Szabo, N. Kedei, F. Bizik, A. P. Kozikowski and P. M. Blumberg, Org. Biomol. Chem., 2004, 2, 2281 DOI: 10.1039/B404506H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements