BIOSYNTHESIS OF ANANDAMIDE--A NOVEL EICOSANOID

此应用程序的主要目标是描述所涉及的过程 在激动剂刺激的花生四烯酸乙醇胺合成中， 完整的细胞 该实验室的初步报告（8）显示， 能够激活磷脂酶以释放游离花生四烯酸的试剂 酸似乎也促进花生四烯酸合成。 此观察结果 提供了我们希望在这方面进行测试的假设的基础。 建议，即花生四烯酸合成生理控制 在于调节细胞磷脂酶活性。 这是 类二十烷酸家族的其他成员的情况， 花生四烯酸是一个新成员。 大麻素被认为是一种假定的内源性拟大麻素 然而，它的重要性可能会超出这个领域。 滥用药物 事实上，有人推测它可能代表了一种 一类新型神经调节剂，因为它的分布和 生物效应。 还观察到结合大麻素的受体 在与免疫系统相关的外周细胞中， 也可能有中枢神经系统以外的功能。 因此， 了解它的组织水平是如何控制的， 一些重要性。 本建议中要解决的具体问题是： 能够刺激大麻素合成的激动剂？ (b)是细胞 （c）在培养适合进行此类研究的实验模型方面， 完整细胞合成所需的受体？ (d)哪种酶 介体负责合成大麻素？ (e)有哪些 细胞合成大麻素的重要前体 根据对花生四烯酸的性质的了解，它的重要性可能 它参与了控制中枢神经系统的新的神经调节过程 情绪、运动协调、认知能力、时间感等功能 和自我认知 此外，外围效应对 心血管、免疫、内分泌和呼吸系统也可能是 anandamides的活动范围。 拟议的研究可提供 发展疾病治疗方法的有用模型 例如多发性硬化症、亨廷顿氏病等，其中使用 大麻素已经被研究过了。 用于控制内源性的方法 在体内合成大麻素可以证明是有益的， 这类疾病的症状。 最后，有可能 花生四烯酸酰胺只是调节剂家族中的一员， 该项目产生的数据将提供证据证明存在 其他更有效或更具体的“花生四烯酸酰胺”。

The main goal of this application is to characterize the process involved in agonist-stimulated synthesis of anandamide (arachidonylethanolamine) in intact cells. A preliminary report (8) from this laboratory showed that agents capable of activating phospholipases to release free arachidonic acid appear to also promote anandamide synthesis. This observation has provided the basis for the hypothesis that we wish to test in this proposal, namely, that physiological control of anandamide synthesis resides in the regulation of cellular phospholipase activity. This is the situation for the other members of the eicosanoid family of which anandamide is a novel member. Anandamide has been suggested to be a putative endogenous cannabimimetic substance, however, its significance will probably extend beyond the area of drug abuse. Indeed, it has been speculated that it may represent a class of novel neuroregulatory agents because of its distribution and biological effects. Receptors that bind anandamide have also been observed in peripheral cells associated with the immune system suggesting that it may have functions outside of the central nervous system as well. Thus, an understanding of how its tissue levels are controlled becomes a matter of some importance. Specific questions to be addressed in this proposal are; (a) What are the agonists that are able to stimulate anandamide synthesis? (b) Are cells in culture suitable experimental models for such studies; (c) Are receptors required for synthesis in intact cells? (d) Which enzymic mediators are responsible for anandamide synthesis? (e) What are the important precursors for cellular anandamide synthesis? Based on what is known about anandamide's properties, its significance may be that it is involved in novel neuroregulatory processes that control CNS functions such as mood, motor coordination, cognitive ability, time-sense and self-perception. In addition, peripheral effects on the cardiovascular, immune, endocrine and respiratory systems may also be part of anandamides' spectrum of activities. The proposed studies may provide useful models for the development of therapeutic approaches to diseases such as multiple sclerosis, Huntington's, etc. where the use of cannabinoids has been explored. Methods for controlling endogenous anandamide synthesis in vivo could prove to be beneficial in relieving the symptoms of these types of ailments. Finally, it is possible that anandamide is only one member of a family of regulatory agents and that data resulting from this project will provide evidence for the existence of other more potent or specific "anandamides".