Biosynthesis and degradation of bioactive fatty acid amides in human breast cancer and rat pheochromocytoma cells

作者：Tiziana Bisogno, Kazuhisa Katayama, Dominique J. Melck, Natsuo Ueda, Luciano De Petrocellis, Shozo Yamamoto, Vincenzo Di Marzo · 发表于：European Journal of Biochemistry · 年份：1998 · DOI：10.1046/j.1432-1327.1998.2540634.x · 被引用次数：99 · 研究领域：Cannabis and Cannabinoid Research、Diet, Metabolism, and Disease、Alcohol Consumption and Health Effects

The endogenous cannabinoid, anandamide (arachidonoylethanolamide), and the sleep-inducing factor, oleamide (cis-9-octadecenoamide), represent two classes of long-chain fatty acid amides with several neuronal actions and metabolic pathways in common. Here we report that these two compounds are present in human breast carcinoma EFM-19 cells and rat adrenal pheochromocytoma PC-12 cells, together with the enzyme responsible for their degradation, fatty acid amide hydrolase, and the proposed biosynthetic precursors for arachidonoylethanolamide and related acylethanolamides, the N-acyl-phosphatidylethanolamines. Lipids extracted from cells labelled with [14C]ethanolamine contained radioactive compounds with the same chromatographic behaviour as arachidonoylethanolamide and acyl-PtdEtns. The levels of these compounds were not influenced by either stimulation with ionomycin in EFM-19 cells or two-week treatment with the nerve growth factor in PC-12 cells. The chemical nature of arachidonoylethanolamide, related acylethanolamides and the corresponding acyl-PtdEtns was confirmed by gas chromatographic/mass spectrometric analyses of the purified compounds, which also showed the presence of higher levels of oleamide. The latter compound, which does not activate the central CB1 cannabinoid receptor, exhibited an anti-proliferative action on EFM-19 cells at higher concentrations than arachidonoylethanolamide (IC50 = 11.3 microM for oleamide and 2.1 microM for arachidonoylethanolamide), whi...