Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Riera, CE; Menozzi-Smarrito, C; Affolter, M; Michlig, S; Munari, C; Robert, F; Vogel, H; Simon, SA; le Coutre, J

Published Date

  • August 2009

Published In

Volume / Issue

  • 157 / 8

Start / End Page

  • 1398 - 1409

PubMed ID

  • 19594761

Pubmed Central ID

  • 19594761

Electronic International Standard Serial Number (EISSN)

  • 1476-5381

Digital Object Identifier (DOI)

  • 10.1111/j.1476-5381.2009.00307.x

Language

  • eng

Conference Location

  • England