Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes - Comparison with synthesis from free arachidonic acid and ethanolamine

被引：185

作者：

Sugiura, T ^{[1
]}

Kondo, S ^{[1
]}

Sukagawa, A ^{[1
]}

Tonegawa, T ^{[1
]}

Nakane, S ^{[1
]}

Yamashita, A ^{[1
]}

Ishima, Y ^{[1
]}

Waku, K ^{[1
]}

机构：

[1] ISHIMA INST NEUROSCI,TOKYO,JAPAN

来源：

EUROPEAN JOURNAL OF BIOCHEMISTRY | 1996年 / 240卷 / 01期

关键词：

anandamide (N-arachidonoylethanolamine); N-arachidonoylphosphatidylethanolamine; cannabinoid; transacylase; phosphodiesterase;

D O I：

10.1111/j.1432-1033.1996.0053h.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：53 / 62

页数：10

共 46 条

[1] (R)-METHANANDAMIDE - A CHIRAL NOVEL ANANDAMIDE POSSESSING HIGHER POTENCY AND METABOLIC STABILITY [J].