title: Naturally Produced Defensive Alkenal Compounds Activate TRPA1.
abstract: (E)-2-alkenals are aldehydes containing an unsaturated bond between the alpha and beta carbons. 2-alkenals are produced by many organisms for defense against predators and secretions containing (E)-2-alkenals cause predators to stop attacking and allow the prey to escape. Chemical ecologists have described many alkenal compounds with 3-20 carbons common, having varied positions of double bonds and substitutions. How do these defensive alkenals act to deter predators? We have tested the effects of (E)-2-alkenals with 6-12 carbons on transient receptor potential channels (TRP) commonly found in sensory neurons. We find that (E)-2-alkenals activate transient receptor potential ankyrin subtype 1 (TRPA1) at low concentrations-EC50s 10-100 µM (in 0 added Ca(2+) external solutions). Other TRP channels were either weakly activated (TRPV1, TRPV3) or insensitive (TRPV2, TRPV4, TRPM8). (E)-2-alkenals may activate TRPA1 by modifying cysteine side chains. However, target cysteines include others beyond the 3 in the amino-terminus implicated in activation, as a channel with cysteines at 621, 641, 665 mutated to serine responded robustly. Related chemicals, including the aldehydes hexanal and decanal, and (E)-2-hexen-1-ol also activated TRPA1, but with weaker potency. Rat trigeminal nerve recordings and behavioral experiments showed (E)-2-hexenal was aversive. Our results suggest that TRPA1 is likely a major target of these commonly used defensive chemicals.
authors: Howard Hughes Medical Institute (HHMI), Boston, MA, USA, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors: Nathaniel T
authors: NT
authors: Blair
authors: Harvard College, Cambridge, MA 02138, USA.
authors: Benjamin I
authors: BI
authors: Philipson
authors: Department of Biology, Wake Forest University, Winston-Salem, NC 27106, USA and.
authors: Paige M
authors: PM
authors: Richards
authors: Howard Hughes Medical Institute (HHMI), Boston, MA, USA, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors: Julia F
authors: JF
authors: Doerner
authors: Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Abraham
authors: A
authors: Segura
authors: Department of Biology, Wake Forest University, Winston-Salem, NC 27106, USA and.
authors: Wayne L
authors: WL
authors: Silver
authors: Howard Hughes Medical Institute (HHMI), Boston, MA, USA, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA, dclapham@enders.tch.harvard.edu.
authors: David E
authors: DE
authors: Clapham
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D057809:HEK293 Cells; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D000441:Hexanols / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D000447:Aldehydes; D015220:Calcium Channels; D000441:Hexanols; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C051750:2-hexenal; C037076:2-hexanol; D003545:Cysteine; D002118:Calcium
keywords: allomone; chemoreception; deterrent; nociceptor; trigeminal sensation