title: Activation of transient receptor potential A1 by a non-pungent capsaicin-like compound, capsiate.
abstract: OBJECTIVE
  Capsiate is produced by 'CH-19 Sweet' (Capsicum annuun L.), a non-pungent cultivar of red pepper. Like capsaicin, capsiate is thought to enhance energy metabolism by activating the sympathetic nervous system and suppressing inflammation, but the underlying mechanisms for this are uncertain. We previously reported that capsiate could activate transient receptor potential vanilloid 1 (TRPV1), a capsaicin receptor. The purpose of the present study is to investigate whether capsinoids activate other TRP channels.
  
  
  METHODS
  Using Ca(2+) imaging and whole-cell patch-clamp methods, we analysed the response of TRP channels to three kinds of capsinoids, capsiate, dihydrocapsiate and nordihydrocapsiate, in HEK293T cells expressing TRP channels or in primary cultures of mouse dorsal root ganglion neurons.
  
  
  RESULTS
  We found that in both cell types TRP ankyrin 1 (TRPA1) had a slightly weaker response to capsinoids compared with TRPV1, with the capsiate EC(50) for TRPA1 activation being more than that for TRPV1 activation, and that the capsinoid-evoked action was blocked by a specific TRPA1 antagonist. TRPA1 was activated by capsinoids, but not by their degradation products. Amino acids known to participate in TRPA1 activation following cysteine covalent modification or zinc treatment were not involved in the activation of TRPA1 by capsinoid.
  
  
  CONCLUSIONS
  Taken together, these results indicate that capsinoids activate TRPA1 by an as yet unknown mechanism, and TRPA1 could be involved in physiological phenomena associated with capsinoid treatment.
authors: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
authors: Kenji
authors: K
authors: Shintaku
authors: Kunitoshi
authors: K
authors: Uchida
authors: Yoshiro
authors: Y
authors: Suzuki
authors: Yiming
authors: Y
authors: Zhou
authors: Tohru
authors: T
authors: Fushiki
authors: Tatsuo
authors: T
authors: Watanabe
authors: Susumu
authors: S
authors: Yazawa
authors: Makoto
authors: M
authors: Tominaga
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002212:Capsicum / Q000737:chemistry; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
chemical_list: D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C004471:allyl isothiocyanate; D015032:Zinc; C470213:capsiate; D002211:Capsaicin; D002118:Calcium