Boger D L, Henriksen S J, Cravatt B F
Department of Chemistry, Scripps Research Institute, La Jolla, California 92037, USA.
Curr Pharm Des. 1998 Aug;4(4):303-14.
Oleamide is an endogenous fatty acid primary amide that accumulates in the cerebrospinal fluid under conditions of sleep deprivation and induces physiological sleep in animals. A review covering its discovery, its implications, and the emerging biology surrounding its discovery is presented. Consistent with its role as a prototypical member of a new class of biological signaling molecules, enzymatic regulation of endogenous concentrations of oleamide have been characterized or proposed. Fatty acid amide hydrolase (FAAH) is an integral membrane protein that degrades oleamide and potent inhibitors with physiological sleep-inducing properties have been disclosed. The characterization, cloning, and neuronal distribution of FAAH have been detailed and the enzyme was found to possess the ability to hydrolyze a range of fatty acid amides including anandamide which serves as the endogenous ligand for the cannabinoid receptor. An additional endogenous substance with REM sleep-inducing properties, 2-octyl gamma-bromoacetoacetate, was characterized as a potent FAAH inhibitor. Oleamide has been shown to modulate serotonergic neurotransmission and inhibit intercellular gap junction communication and detailed studies of its well defined and selective structural features required for activity have been disclosed.
油酰胺是一种内源性脂肪酸一级酰胺，在睡眠剥夺条件下会在脑脊液中蓄积，并在动物体内诱导生理性睡眠。本文综述了其发现过程、意义以及围绕其发现所涌现出的生物学研究。与其作为一类新型生物信号分子的原型成员的作用相一致，对内源性油酰胺浓度的酶促调节已得到表征或提出。脂肪酸酰胺水解酶（FAAH）是一种整合膜蛋白，可降解油酰胺，并且已公开了具有生理性睡眠诱导特性的强效抑制剂。FAAH的表征、克隆及神经元分布已详细阐述，发现该酶具有水解一系列脂肪酸酰胺的能力，包括作为大麻素受体内源性配体的花生四烯酸乙醇胺。另一种具有快速眼动睡眠诱导特性的内源性物质2-辛基γ-溴代乙酰乙酸被表征为一种强效FAAH抑制剂。油酰胺已被证明可调节5-羟色胺能神经传递并抑制细胞间缝隙连接通讯，并且已公开了对其活性所需的明确且选择性的结构特征的详细研究。
