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Proc Natl Acad Sci U S A. 2000 May 23;97(11):6155-60.

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

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1
Sensory Research Group, National Creative Research Initiatives, College of Pharmacy, Seoul National University, San 56-1, Shinlim, Kwanak-Gu, Seoul 151-742, Korea.

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 B(4) 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.

PMID:
10823958
PMCID:
PMC18574
[Indexed for MEDLINE]
Free PMC Article
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