Direct activation of capsaicin receptors by products of lipoxygenases: Endogenous capsaicin-like substances

Sun Wook Hwang, Hawon Cho, Jiyeon Kwak, Soon Youl Lee, Chang Joong Kang, Jooyoung Jung, Soohyun Cho, Kyung Hoon Min, Young Ger Suh, Donghee Kim, Uhtaek Oh

Research output: Contribution to journalArticlepeer-review

618 Citations (Scopus)

Abstract

Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)- hydroxyeicosatetraenoic acids, and leukotriene B4 possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.

Original languageEnglish
Pages (from-to)6155-6160
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number11
DOIs
Publication statusPublished - 2000 May 23
Externally publishedYes

ASJC Scopus subject areas

  • General

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