Department of Entomology and University of California Davis Cancer Center, University of California-Davis, Davis, California 95616, United States.
J Agric Food Chem. 2011 Apr 13;59(7):2816-24. doi: 10.1021/jf102559q. Epub 2010 Oct 19.
The soluble epoxide hydrolase (sEH) enzyme was discovered while investigating the metabolism of xenobiotic compounds in the Casida laboratory. However, an endogenous role of sEH is to regulate the levels of a group of potent bioactive lipids, epoxygenated fatty acids (EFAs), that have pleiotropic biological activities. The EFAs, in particular the arachidonic acid derived epoxy eicosatrienoic acids (EETs), are established autocrine and paracrine messengers. The most recently discovered outcome of inhibition of sEH and increased EFAs is their effects on the sensory system and in particular their ability to reduce pain. The inhibitors of sEH block both inflammatory and neuropathic pain. Elevation of EFAs, in both the central and peripheral nervous systems, blocks pain. Several laboratories have now published a number of potential mechanisms of action for the pain-reducing effects of EFAs. This paper provides a brief history of the discovery of the sEH enzyme and argues that inhibitors of sEH through several independent mechanisms display pain-reducing effects.
可溶性环氧化物水解酶（sEH）是在 Casida 实验室研究外源化合物代谢时发现的。然而，sEH 的一个内源性作用是调节一组强效生物活性脂质——环氧脂肪酸（EFAs）的水平，这些脂质具有多种生物学活性。EFAs，特别是源自花生四烯酸的环氧二十碳三烯酸（EETs），是公认的自分泌和旁分泌信使。最近发现的抑制 sEH 和增加 EFAs 的结果是它们对感觉系统的影响，特别是它们减轻疼痛的能力。sEH 的抑制剂可阻断炎症性和神经性疼痛。EFAs 在中枢和周围神经系统中的升高可阻断疼痛。现在有几个实验室已经发表了 EFAs 减轻疼痛作用的一些潜在作用机制。本文简要介绍了 sEH 酶的发现过程，并认为 sEH 的抑制剂通过几种独立的机制显示出减轻疼痛的效果。
