Quantitative LC-MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor
Quantitative LC-MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor
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DOI：
10.1016/j.ab.2012.09.031
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发表时间：
2013-01-15
影响因子：
2.9
通讯作者：
Barker, Eric
中科院分区：
文献类型：
--
作者：
Han, Bingnan;Wright, Rachel;Barker, Eric
另一类内源性脂质酰胺，N-花生四烯酸氨基酸（Ara-AAs），在内源性大麻素领域的重要性日益增加。建立了一种同时监测和定量小鼠脑中Ara-AAs沿着花生四烯酸酰胺（AEA）和2-花生四烯酸甘油（2-AG）水平的灵敏和选择性方法。对于N-花生四烯酸标准品，该方法在0.2-120 pg/μ l浓度范围内呈线性。N-花生四烯酸丙氨酸（NAAla）、丝氨酸（NASer）、γ-氨基丁酸（NAGABA）和甘氨酸（NAGly）; AEA-d（0）/d（8）为0.7-90 pg/μ l; 2-AG为7.5-950 pg/μ l，R-2值为0.99。还研究了FAAH抑制剂URB 597对这些分析物的内源性水平的影响。在全身施用URB 597后，AEA和NASer脑水平表现出剂量依赖性增加，而NAGly和NAGABA在治疗后显著降低。URB 597处理后NAAla和2-AG没有改变。建立该测定法的潜在益处超出了小鼠脑中Ara-AAs沿着AEA和2-AG的定量，以揭示这些分析物的各种药理学作用和生理学作用。(c)2012 Elsevier Inc. All rights reserved.
An additional class of endogenous lipid amides, N-arachidonoyl amino acids (Ara-AAs), is growing in significance in the field of endocannabinoids. The development, validation, and application of a sensitive and selective method to simultaneously monitor and quantify the level of Ara-AAs along with anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in mouse brain has been established. The linearity of the method over the concentration ranges of 0.2-120 pg/mu l for the standards of N-arachidonoyl amino acids. N-arachidonoyl alanine (NAAla), serine (NASer), gamma-aminobutyric acid (NAGABA), and glycine (NAGly); 0.7-90 pg/mu l for AEA-d(0)/d(8); and 7.5-950 pg/mu l for 2-AG was determined with R-2 values of 0.99. Also the effects of the FAAH inhibitor URB 597 on the endogenous levels of these analytes were investigated. AEA and NASer brain levels exhibit a dose-dependent increase after systemic administration of URB 597, whereas NAGly and NAGABA were significantly decreased after treatment. NAAla and 2-AG were not altered after URB 597 treatment. The potential benefit of establishing this assay extends beyond the quantification of the Ara-AAs along with AEA and 2-AG in mouse brain, to reveal a variety of pharmacological effects and physiological roles of these analytes. (c) 2012 Elsevier Inc. All rights reserved.