期刊
ANALYTICAL BIOCHEMISTRY
卷 432, 期 2, 页码 74-81出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2012.09.031
关键词
Arachidonoyl amino acids; Anandamide; 2-Arachidonoyl glycerol; FAAH inhibitor; Brain; LC-MS/MS
资金
- National Institutes of Health [R21 DA024193, R21 DA018112, AA019529, R33DK70290]
- Fundamental Research Funds for the Central Universities of China [2010QNA4014]
- NSF from ZheJiang Province, China [Y2100044]
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.
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