Nestle Research Center, Vers-Chez-Les-Blanc, 1000 Lausanne 26, Switzerland.
J Agric Food Chem. 2009 Mar 11;57(5):1982-9. doi: 10.1021/jf803067r.
Szechuan pepper is widely used in Asia as a spice for its pleasant pungent and tingling sensations, produced by natural alkylamides called sanshools. alpha-Hydroxysanshool, the main alkylamide found in the pericarp of the fruit, stimulates sensory neurons innervating the mouth by targeting two chemosensitive members of the transient receptor potential (TRP) channels, TRPV1 and TRPA1. As it was previously found that configuration of the unsaturations in the alpha-hydroxysanshool alkyl chain is required for TRPA1 but not TRPV1 selectivity, this study aimed at obtaining more potent and selective TRPA1 agonists using alpha-hydroxysanshool as a starting material. This paper reports the preparation of new alkylamides derived from sanshool and their efficacy in stimulating TRPA1 and TRPV1 receptors. The data provide knowledge of the main sanshool chemical functionalities required for TRP channel activation, but they also evidence new selective and potent TRPA1 agonists based on alpha-hydroxysanshool.
花椒在亚洲被广泛用作香料，因其具有令人愉悦的辛辣和刺痛感，这是由天然烷基酰胺（称为山椒素）产生的。α-羟基山椒素是果实种皮中发现的主要烷基酰胺，通过靶向瞬时受体电位 (TRP) 通道中的两个化学敏感成员 TRPV1 和 TRPA1，刺激支配口腔的感觉神经元。由于先前发现 α-羟基山椒素烷基链中的不饱和配置对于 TRPA1 而不是 TRPV1 的选择性是必需的，因此本研究旨在使用 α-羟基山椒素作为起始材料获得更有效和选择性的 TRPA1 激动剂。本文报道了源自山椒素的新烷基酰胺的制备及其刺激 TRPA1 和 TRPV1 受体的功效。这些数据提供了 TRP 通道激活所需的山椒素主要化学功能的知识，但它们也证明了基于 α-羟基山椒素的新的选择性和有效 TRPA1 激动剂。
