Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, Ishima Y, Waku K
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Eur J Biochem. 1996 Aug 15;240(1):53-62. doi: 10.1111/j.1432-1033.1996.0053h.x.
The levels of N-arachidonoylethanolamine (anandamide), an endogenous cannabinoid-receptor ligand, and a relevant molecule, N-arachidonoylphosphatidylethanolamine (N-arachidonoylPtdEtn), in rat brain were investigated using a newly developed sensitive analytical method. We found that rat brain contains small but significant amounts of these two types of N-arachidonoyl lipids (4.3 pmol/g tissue and 50.2 pmol/g tissue, respectively). Then, we investigated how N-arachidonoylethanolamine (anandamide) is produced in the brain. We found that anandamide can be formed enzymatically via two separate synthetic pathways in the brain: enzymatic condensation of free arachidonic acid and ethanolamine; and formation of N-arachidonoylPtdEtn from PtdEtn and arachidonic acid esterified at the 1-position of phosphatidyl-choline (PtdCho), and subsequent release of anandamide from N-arachidonoylPtdEtn through the action of a phosphodiesterase. We confirmed that rat brain contains both the enzyme activities and lipid substrates involved in these reactions. Several lines of evidence strongly suggest that the second pathway, rather than the first one, meets the requirements and conditions for the synthesis of various species of N-acylethanolamine including anandamide in the brain.
使用一种新开发的灵敏分析方法，对大鼠脑中内源性大麻素受体配体N-花生四烯酰乙醇胺（花生四烯酸乙醇胺）以及相关分子N-花生四烯酰磷脂酰乙醇胺（N-花生四烯酰磷脂酰乙醇胺）的水平进行了研究。我们发现大鼠脑含有少量但显著量的这两种类型的N-花生四烯酰脂质（分别为4.3 pmol/g组织和50.2 pmol/g组织）。然后，我们研究了N-花生四烯酰乙醇胺（花生四烯酸乙醇胺）在脑中是如何产生的。我们发现花生四烯酸乙醇胺可通过脑中两条独立的合成途径酶促形成：游离花生四烯酸与乙醇胺的酶促缩合；以及由磷脂酰乙醇胺（PtdEtn）和在磷脂酰胆碱（PtdCho）1位酯化的花生四烯酸形成N-花生四烯酰磷脂酰乙醇胺，随后通过磷酸二酯酶的作用从N-花生四烯酰磷脂酰乙醇胺释放花生四烯酸乙醇胺。我们证实大鼠脑含有参与这些反应的酶活性和脂质底物。几条证据有力地表明，第二条途径而非第一条途径满足脑中包括花生四烯酸乙醇胺在内的各种N-酰基乙醇胺合成的要求和条件。
