Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules.
Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules.
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DOI：
10.2174/138161280404221010152220
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发表时间：
1998-08
影响因子：
3.1
通讯作者：
D. Boger;S. Henriksen;B. Cravatt
中科院分区：
文献类型：
--
作者：
D. Boger;S. Henriksen;B. Cravatt
油酰胺是一种内源性脂肪酸伯酰胺，在睡眠剥夺条件下在脑脊液中积累并诱导动物的生理睡眠。综述了它的发现，它的影响，以及围绕它的发现的新兴生物学。与其作为一类新的生物信号分子的原型成员的作用一致，已经表征或提出了油酰胺内源性浓度的酶促调节。脂肪酸酰胺水解酶（FAAH）是降解油酰胺的整合膜蛋白，并且已经公开了具有生理睡眠诱导性质的有效抑制剂。FAAH的表征、克隆和神经元分布已被详细描述，并且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的内源性配体的大麻素酰胺。另一种具有REM睡眠诱导特性的内源性物质2-辛基γ-溴乙酰乙酸酯被表征为有效的FAAH抑制剂。油酰胺已显示出调节多巴胺能神经传递并抑制细胞间间隙连接通讯，并且已经公开了对其活性所需的明确定义和选择性结构特征的详细研究。
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.