Activation of transient receptor potential A1 by a non-pungent capsaicin-like compound, capsiate.

Abstract

BACKGROUND AND PURPOSE:

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.

EXPERIMENTAL APPROACH:

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.

KEY 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 AND IMPLICATIONS:

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: Kenji Shintaku, Kunitoshi Uchida, Yoshiro Suzuki, Yiming Zhou, Tohru Fushiki, Tatsuo Watanabe, Susumu Yazawa, Makoto Tominaga
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 165 Issue 5 Pg. 1476-86 (Mar 2012) ISSN: 1476-5381 [Electronic] England
• PMID: 21883144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• Isothiocyanates
• TRPA1 Cation Channel
• TRPV Cation Channels
• TRPV1 protein, mouse
• Transient Receptor Potential Channels
• Trpa1 protein, mouse
• allyl isothiocyanate
• Zinc
• capsiate
• Capsaicin
• Calcium

Topics

• Animals
• Binding Sites (drug effects)
• Calcium (metabolism)
• Capsaicin (analogs & derivatives, pharmacology)
• Capsicum (chemistry)
• Cells, Cultured
• Cytosol (drug effects, metabolism)
• Ganglia, Spinal (drug effects, metabolism)
• HEK293 Cells
• Humans
• Isothiocyanates (pharmacology)
• Male
• Membrane Potentials (drug effects)
• Mice
• Mice, Inbred C57BL
• Neurons (drug effects, metabolism)
• TRPA1 Cation Channel
• TRPV Cation Channels (metabolism)
• Transient Receptor Potential Channels (antagonists & inhibitors, metabolism)
• Zinc (pharmacology)