5,6-EET is released upon neuronal activity and induces mechanical pain hypersensitivity via TRPA1 on central afferent terminals.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Marco SisignanoChristian Brenneis

Abstract

Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution of 5,6-EET to transient receptor potential (TRP) channel activation in nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced nociception, 5,6-EET levels increased in dorsal root ganglia (DRGs) and the dorsal spinal cord, and 5,6-EET is released from activated sensory neurons in vitro. 5,6-EET potently induced a calcium flux (100 nm) in cultured DRG neurons that was completely abolished when TRPA1 was deleted or inhibited. In spinal cord slices, 5,6-EET dose dependently enhanced the frequency, but not the amplitude, of spontaneous EPSCs (sEPSCs) in lamina II neurons that also responded to mustard oil (allyl isothiocyanate), indicating a presynaptic action. Furthermore, 5,6-EET-induced enhancement of sEPSC frequency was abolished in TRPA1-null mice, suggesting that 5,6-EET presynaptically facilitated spinal cord synaptic transmission by TRPA1. Finally, in vivo intrathecal injection of 5,6-EET caused mechanical allodynia in wild-type but not TRPA1-nul...Continue Reading

References

Apr 17, 2002·Journal of Neurology·Stefan Quasthoff, Hans Peter Hartung
Dec 5, 2003·Nature·David E Clapham
May 7, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicole Alessandri-HaberJon D Levine
Apr 28, 2005·Cancer Chemotherapy and Pharmacology·Daniel L GustafsonPatrick J Kerzic
Sep 2, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Haibin WangClifford J Woolf
Feb 24, 2006·Hypertension·Ingrid Fleming, Rudi Busse
Jun 17, 2006·Annual Review of Neuroscience·Ajay DhakaArdem Patapoutian
Sep 22, 2006·American Journal of Physiology. Cell Physiology·Arthur A Spector, Andrew W Norris
May 12, 2007·American Journal of Physiology. Renal Physiology·Rolf M NüsingMarkus Wegmann
Jul 12, 2007·The Biochemical Journal·Robert C Murphy, Miguel A Gijón
Aug 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Marcello TrevisaniPierangelo Geppetti
Aug 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Colleen R McNamaraChristopher M Fanger
Apr 10, 2008·The Journal of Clinical Investigation·Bret F BessacSven-Eric Jordt
Aug 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Serena MaterazziPierangelo Geppetti
Sep 23, 2008·The Journal of Biological Chemistry·Ovidiu CosteKlaus Scholich
Jan 1, 2009·Nature Reviews. Drug Discovery·Ardem PatapoutianClifford J Woolf
Apr 17, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kelvin Y KwanCheryl L Stucky
Oct 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Amol M PatwardhanKenneth M Hargreaves
Apr 29, 2010·The Journal of Clinical Investigation·Amol M PatwardhanKenneth M Hargreaves
Nov 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Donato del CaminoMagdalene M Moran
Oct 6, 2011·Molecular Pain·Christian BrenneisKlaus Scholich

❮ Previous
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Citations

Sep 25, 2012·Pflügers Archiv : European journal of physiology·Bernd NiliusGrzegorz Owsianik
Aug 29, 2012·PloS One·Richard C LennertzCheryl L Stucky
Nov 30, 2013·Progress in Lipid Research·Marco SisignanoKlaus Scholich
Jun 12, 2013·Pflügers Archiv : European journal of physiology·David C EllinsworthShaun L Sandow
Apr 12, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·Gabriela TrevisanJuliano Ferreira
Apr 18, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sungjae YooSun Wook Hwang
Aug 11, 2012·Current Rheumatology Reports·Susan L MurphyDaniel J Clauw
Sep 19, 2014·International Journal of Molecular Sciences·Seung-In ChoiSun Wook Hwang
Sep 11, 2013·Basic & Clinical Pharmacology & Toxicology·Karin MeirerEwgenij Proschak
Dec 7, 2013·British Journal of Pharmacology·Shijin YinHongzhen Hu
Nov 29, 2013·British Journal of Pharmacology·J Sousa-ValenteI Nagy
Nov 3, 2015·Toxicology and Applied Pharmacology·Sumanta Kumar GoswamiBruce D Hammock
Aug 22, 2015·Der Schmerz·E NiederbergerG Geißlinger
Apr 4, 2015·Biochimica Et Biophysica Acta·Francisco J TabernerAntonio Ferrer-Montiel
Feb 3, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·Jun Chen, David H Hackos
May 29, 2013·Pain·David B ReichlingJon D Levine
Jun 11, 2016·Drug Metabolism Reviews·Michael Murray
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Marco SisignanoGerd Geisslinger
Apr 23, 2017·Biochimica Et Biophysica Acta. Biomembranes·Maria Grazia Ciardo, Antonio Ferrer-Montiel
Jun 10, 2017·Nature Reviews. Drug Discovery·Ajay S YekkiralaClifford J Woolf
Dec 7, 2017·Frontiers in Cellular Neuroscience·Meiyan JiangPeter S Steyger
Mar 1, 2017·The Journal of Biological Chemistry·Sebastian ZinnKlaus Scholich
Nov 2, 2019·Physiological Reviews·Karel TalaveraBernd Nilius
Feb 2, 2019·The Journal of Headache and Pain·Doga VuralliHayrunnisa Bolay

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