PMID- 19594761
OWN - NLM
STAT- MEDLINE
DCOM- 20100112
LR  - 20240109
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 157
IP  - 8
DP  - 2009 Aug
TI  - Compounds from Sichuan and Melegueta peppers activate, covalently and 
      non-covalently, TRPA1 and TRPV1 channels.
PG  - 1398-409
LID - 10.1111/j.1476-5381.2009.00307.x [doi]
AB  - BACKGROUND AND PURPOSE: Oily extracts of Sichuan and Melegueta peppers evoke 
      pungent sensations mediated by different alkylamides [mainly 
      hydroxy-alpha-sanshool (alpha-SOH)] and hydroxyarylalkanones (6-shogaol and 
      6-paradol). We assessed how transient receptor potential ankyrin 1 (TRPA1) and 
      TRP vanilloid 1 (TRPV1), two chemosensory ion channels, participate in these 
      pungent sensations. EXPERIMENTAL APPROACH: The structure-activity relationships 
      of these molecules on TRPA1 and TRPV1 was measured by testing natural and 
      synthetic analogues using calcium and voltage imaging on dissociated dorsal root 
      ganglia neurons and human embryonic kidney 293 cells expressing the wild-type 
      channels or specific cysteine mutants using glutathione trapping as a model to 
      probe TRPA1 activation. In addition, using Trpv1 knockout mice, the compounds' 
      aversive responses were measured in a taste brief-access test. KEY RESULTS: For 
      TRPA1 activation, the cis C6 double bond in the polyenic chain of alpha-SOH was 
      critical, whereas no structural specificity was required for activation of TRPV1. 
      Both 6-shogaol and 6-paradol were found to activate TRPV1 and TRPA1 channels, 
      whereas linalool, an abundant terpene in Sichuan pepper, activated TRPA1 but not 
      TRPV1 channels. Alkylamides and 6-shogaol act on TRPA1 by covalent bonding 
      whereas none of these compounds activated TRPV1 through such interactions. 
      Finally, TRPV1 mutant mice retained sensitivity to 6-shogaol but were not 
      responsive to alpha-SOH. CONCLUSIONS AND IMPLICATIONS: The pungent nature of 
      components of Sichuan and Melegueta peppers was mediated via interactions with 
      TRPA1 and TRPV1 channels and may explain the aversive properties of these 
      compounds.
FAU - Riera, C E
AU  - Riera CE
AD  - Nestle Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland.
FAU - Menozzi-Smarrito, C
AU  - Menozzi-Smarrito C
FAU - Affolter, M
AU  - Affolter M
FAU - Michlig, S
AU  - Michlig S
FAU - Munari, C
AU  - Munari C
FAU - Robert, F
AU  - Robert F
FAU - Vogel, H
AU  - Vogel H
FAU - Simon, S A
AU  - Simon SA
FAU - le Coutre, J
AU  - le Coutre J
LA  - eng
PT  - Journal Article
DEP - 20090708
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Amides)
RN  - 0 (Catechols)
RN  - 0 (Ketones)
RN  - 0 (Plant Oils)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 0 (Transient Receptor Potential Channels)
RN  - 0 (Trpa1 protein, mouse)
RN  - 504-97-2 (sanshool)
RN  - 6JKA7MAH9C (Guaiacol)
RN  - 83DNB5FIRF (shogaol)
RN  - BO24ID7E9U (6-paradol)
SB  - IM
MH  - Amides/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Catechols/pharmacology
MH  - Cells, Cultured
MH  - Female
MH  - Guaiacol/analogs & derivatives/pharmacology
MH  - Humans
MH  - Ketones/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Plant Oils/*chemistry/*pharmacology
MH  - Structure-Activity Relationship
MH  - TRPA1 Cation Channel
MH  - TRPV Cation Channels/*agonists/genetics/metabolism
MH  - Transient Receptor Potential Channels/*agonists/genetics/metabolism
MH  - Zanthoxylum/*chemistry
MH  - Zingiberaceae/*chemistry
PMC - PMC2765304
EDAT- 2009/07/15 09:00
MHDA- 2010/01/13 06:00
PMCR- 2010/08/01
CRDT- 2009/07/15 09:00
PHST- 2009/07/15 09:00 [entrez]
PHST- 2009/07/15 09:00 [pubmed]
PHST- 2010/01/13 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - BPH307 [pii]
AID - 10.1111/j.1476-5381.2009.00307.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2009 Aug;157(8):1398-409. doi: 10.1111/j.1476-5381.2009.00307.x. 
      Epub 2009 Jul 8.