[Abstract Title]. - Society for Neuroscience

Topic: D.08.b. Nociceptors
Support: NIH Predoctoral Fellowship F31
Title: TRPA1 mediates the noxious effects of sesquiterpene deterrents
Authors: *J. J. ESCALERA, C. A. VON HEHN, B. F. BESSAC, M. SIVULA, S.-E. JORDT;
Pharmacol., Yale Univ., New Haven, CT
Abstract: Plants, fungi and animals generate a diverse array of deterrent natural products that
induce avoidance behavior in biological adversaries. The largest known chemical family of
deterrents are terpenes characterized by reactive α,β-unsaturated dialdehyde moieties, including
the drimane sesquiterpenes and other terpene species. Deterrent sesquiterpenes are potent
activators of mammalian peripheral chemosensory neurons, causing pain and neurogenic
inflammation. Despite of their widespread synthesis and medicinal use as desensitizing
analgesics their molecular targets remain unknown. Here we show that isovelleral, a noxious
fungal sesquiterpene, excites sensory neurons through activation of TPRA1, an ion channel
involved in inflammatory pain signaling. TRPA1 is also activated by polygodial, a drimane
sesquiterpene synthesized by plants and animals. TRPA1-deficient mice show greatly reduced
nocifensive behavior in response to isovelleral, indicating that TRPA1 is the major receptor for
deterrent sesquiterpenes in vivo. Isovelleral and polygodial represent the first fungal and animal
small molecule agonists of nociceptive TRP channels.
Disclosures: J.J. Escalera, None; C.A. von Hehn, None; B.F. Bessac, None; M. Sivula,
None; S. Jordt, None.
Poster
265. Nociceptors II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 265.8/EE9
Topic: D.08.a. Pain transduction molecules and channels
Support: Brain Research Center of the 21st Century Frontier Research Program (code
M103KV010015-06K2201-01510) funded by the Ministry of Science and Technology, the
Republic of Korea
The Korea Health 21 R&D Project (code A060341) funded by Ministry of Health and
Welfare, the Republic of Korea