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

作者：Shintaku Kenji; Uchida Kunitoshi; Suzuki Yoshiro; Zhou Yiming; Fushiki Tohru; Watanabe Tatsuo; Yazawa Susumu; Tominaga Makoto^*

来源：British Journal of Pharmacology, 2012, 165(5): 1476-1486.

DOI：10.1111/j.1476-5381.2011.01634.x

• capsinoid
• capsiate
• TRPA1 channel
• TRPV1 channel
• patch-clamp
• Ca2+imaging

BACKGROUND AND PURPOSE %26lt;br%26gt;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. %26lt;br%26gt;EXPERIMENTAL APPROACH %26lt;br%26gt;Using Ca2+ 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. %26lt;br%26gt;KEY RESULTS %26lt;br%26gt;We found that in both cell types TRP ankyrin 1 (TRPA1) had a slightly weaker response to capsinoids compared with TRPV1, with the capsiate EC50 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. %26lt;br%26gt;CONCLUSIONS AND IMPLICATIONS %26lt;br%26gt;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.

• 出版日期2012-3