Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1 , TRPM , TRPM8 , TRPV , TRPV1

Title: Activation and inhibition of thermosensitive TRP channels by voacangine, an alkaloid present in Voacanga africana, an African tree.

Authors: Yuko Terada, Syunji Horie, Hiromitsu Takayama, Kunitoshi Uchida, Makoto Tominaga, Tatsuo Watanabe

Journal, date & volume: J. Nat. Prod., 2014 Feb 28 , 77, 285-97

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24484240

Abstract
Voacangine (1) is an alkaloid found in the root bark of Voacanga africana. Our previous work has suggested that 1 is a novel transient receptor potential vanilloid type 1 (TRPV1) antagonist. In this study, the agonist and antagonist activities of 1 were examined against thermosensitive TRP channels. Channel activity was evaluated mainly using TRP channel-expressing HEK cells and calcium imaging. Herein, it was shown that 1 acts as an antagonist for TRPV1 and TRPM8 but as an agonist for TRPA1 (EC50, 8 μM). The compound competitively blocked capsaicin binding to TRPV1 (IC50, 50 μM). Voacangine (1) competitively inhibited the binding of menthol to TRPM8 (IC50, 9 μM), but it showed noncompetitive inhibition against icilin (IC50, 7 μM). Moreover, the compound selectively abrogated chemical agonist-induced TRPM8 activation and did not affect cold-induced activation. Among these effects, the TRPM8 inhibition profile is unique and noteworthy, because to date no studies have reported a menthol competitive inhibitor of TRPM8 derived from a natural source. Furthermore, this is the first report of a stimulus-selective TRPM8 antagonist. Accordingly, 1 may contribute to the development of a novel class of stimulus-selective TRPM8 blockers.