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PNAS 97 (11): 6155-6160

Copyright © 2000 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / NEUROBIOLOGY

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{dagger}, Young-Ger Suh{dagger}, Donghee Kim{ddagger}, and Uhtaek Oh*,§

*Sensory Research Group, National Creative Research Initiatives, {dagger}Division of Medicinal Chemistry, College of Pharmacy, Seoul National University, San 56-1, Shinlim, Kwanak-Gu, Seoul 151-742, Korea; and {ddagger}Department of Physiology and Biophysics, Finch University of Health Sciences/The Chicago Medical School, North Chicago, IL 60064

Received for publication July 16, 1999.

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.


§ To whom reprint requests should be addressed. E-mail: utoh{at}plaza.snu.ac.kr.

Edited by Julius Axelrod, National Institutes of Health, Bethesda, MD, and approved March 17, 2000

This paper was submitted directly (Track II) to the PNAS office.

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   Abstract »    Full Text »    PDF »
Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs.
R. Gatti, E. Andre, S. Amadesi, T. Q. Dinh, A. Fischer, N. W. Bunnett, S. Harrison, P. Geppetti, and M. Trevisani (2006)
J Appl Physiol 101, 506-511
   Abstract »    Full Text »    PDF »
Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs.
B. J. Canning, D. G. Farmer, and N. Mori (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R454-R463
   Abstract »    Full Text »    PDF »
Transient Receptor Potential Channels in Cardiovascular Function and Disease.
R. Inoue, L. J. Jensen, J. Shi, H. Morita, M. Nishida, A. Honda, and Y. Ito (2006)
Circ. Res. 99, 119-131
   Abstract »    Full Text »    PDF »
Tactile Allodynia Initiated by Local Subcutaneous Endothelin-1 Is Prolonged by Activation of TRPV-1 Receptors.
K. Balonov, A. Khodorova, and G. R. Strichartz (2006)
Experimental Biology and Medicine 231, 1165-1170
   Abstract »    Full Text »    PDF »
Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs.
D. R. Bergren (2006)
J Appl Physiol 100, 1918-1927
   Abstract »    Full Text »    PDF »
Ethanol dilates coronary arteries and increases coronary flow via transient receptor potential vanilloid 1 and calcitonin gene-related peptide.
D. Gazzieri, M. Trevisani, F. Tarantini, P. Bechi, G. Masotti, G. F. Gensini, S. Castellani, N. Marchionni, P. Geppetti, and S. Harrison (2006)
Cardiovasc Res 70, 589-599
   Abstract »    Full Text »    PDF »
Kinetics of Penetration Influence the Apparent Potency of Vanilloids on TRPV1.
J. Lazar, D. C. Braun, A. Toth, Y. Wang, L. V. Pearce, V. A. Pavlyukovets, P. M. Blumberg, S. H. Garfield, S. Wincovitch, H.-K. Choi, et al. (2006)
Mol. Pharmacol. 69, 1166-1173
   Abstract »    Full Text »    PDF »
TRPV1 Recapitulates Native Capsaicin Receptor in Sensory Neurons in Association with Fas-Associated Factor 1.
S. Kim, C. Kang, C. Y. Shin, S. W. Hwang, Y. D. Yang, W. S. Shim, M.-Y. Park, E. Kim, M. Kim, B.-M. Kim, et al. (2006)
J. Neurosci. 26, 2403-2412
   Abstract »    Full Text »    PDF »
Multiple eicosanoid-activated nonselective cation channels regulate B-lymphocyte adhesion to integrin ligands.
X. Liu, P. Zhu, and B. D. Freedman (2006)
Am J Physiol Cell Physiol 290, C873-C882
   Abstract »    Full Text »    PDF »
Phosphorylation-Dependent Desensitization by Anandamide of Vanilloid Receptor-1 (TRPV1) Function in Rat Skeletal Muscle Arterioles and in Chinese Hamster Ovary Cells Expressing TRPV1.
E. Lizanecz, Z. Bagi, E. T. Pasztor, Z. Papp, I. Edes, N. Kedei, P. M. Blumberg, and A. Toth (2006)
Mol. Pharmacol. 69, 1015-1023
   Abstract »    Full Text »    PDF »
Novel Compounds That Interact with Both Leukotriene B4 Receptors and Vanilloid TRPV1 Receptors.
D. McHugh, R. S. McMaster, R. G. Pertwee, S. Roy, A. Mahadevan, R. K. Razdan, and R. A. Ross (2006)
J. Pharmacol. Exp. Ther. 316, 955-965
   Abstract »    Full Text »    PDF »
Systemic and Site-Specific Effects of A-425619, a Selective TRPV1 Receptor Antagonist, on Wide Dynamic Range Neurons in CFA-Treated and Uninjured Rats.
S. McGaraughty, K. L. Chu, C. R. Faltynek, and M. F. Jarvis (2006)
J Neurophysiol 95, 18-25
   Abstract »    Full Text »    PDF »
Attenuation of acid induced oesophagitis in VR-1 deficient mice.
K Fujino, S G de la Fuente, Y Takami, T Takahashi, and C R Mantyh (2006)
Gut 55, 34-40
   Abstract »    Full Text »    PDF »
TRPV1 Antagonists Elevate Cell Surface Populations of Receptor Protein and Exacerbate TRPV1-Mediated Toxicities in Human Lung Epithelial Cells.
M. E. Johansen, C. A. Reilly, and G. S. Yost (2006)
Toxicol. Sci. 89, 278-286
   Abstract »    Full Text »    PDF »
Downregulation of Transient Receptor Potential Melastatin 8 by Protein Kinase C-Mediated Dephosphorylation.
L. S. Premkumar, M. Raisinghani, S. C. Pingle, C. Long, and F. Pimentel (2005)
J. Neurosci. 25, 11322-11329
   Abstract »    Full Text »    PDF »
Leukotriene B4 signaling through NF-{kappa}B-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia.
M. Back, D.-x. Bu, R. Branstrom, Y. Sheikine, Z.-Q. Yan, and G. K. Hansson (2005)
PNAS 102, 17501-17506
   Abstract »    Full Text »    PDF »
Endogenous Unsaturated C18 N-Acylethanolamines Are Vanilloid Receptor (TRPV1) Agonists.
P. Movahed, B. A. G. Jonsson, B. Birnir, J. A. Wingstrand, T. D. Jorgensen, A. Ermund, O. Sterner, P. M. Zygmunt, and E. D. Hogestatt (2005)
J. Biol. Chem. 280, 38496-38504
   Abstract »    Full Text »    PDF »
Camphor Activates and Strongly Desensitizes the Transient Receptor Potential Vanilloid Subtype 1 Channel in a Vanilloid-Independent Mechanism.
H. Xu, N. T. Blair, and D. E. Clapham (2005)
J. Neurosci. 25, 8924-8937
   Abstract »    Full Text »    PDF »
Activation of transient receptor potential vanilloid 1 (TRPV1) by resiniferatoxin.
M. Raisinghani, R. M Pabbidi, and L. S Premkumar (2005)
J. Physiol. 567, 771-786
   Abstract »    Full Text »    PDF »
Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1 channels.
M. van der Stelt, M. Trevisani, V. Vellani, L. De Petrocellis, A. Schiano Moriello, B. Campi, P. McNaughton, P. Geppetti, and V. Di Marzo (2005)
EMBO J. 24, 3026-3037
   Abstract »    Full Text »    PDF »
Role of Transient Receptor Potential Vanilloid 1 Receptors in Adjuvant-Induced Chronic Arthritis: In Vivo Study Using Gene-Deficient Mice.
A. Szabo, Z. Helyes, K. Sandor, A. Bite, E. Pinter, J. Nemeth, A. Banvolgyi, K. Bolcskei, K. Elekes, and J. Szolcsanyi (2005)
J. Pharmacol. Exp. Ther. 314, 111-119
   Abstract »    Full Text »    PDF »

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