Multiple pathways involved in the biosynthesis of anandamide

被引：210

作者：

Liu, Jie ^{[1
]}

Wang, Lei ^{[1
]}

Harvey-White, Judith ^{[1
]}

Huang, Bill X. ^{[2
]}

Kim, Hee-Yong ^{[2
]}

Luquet, Serge ^{[3
]}

Palmiter, Richard D. ^{[3
]}

Krystal, Gerald ^{[4
]}

Rai, Ravi ^{[5
]}

Mahadevan, Anu ^{[5
]}

Razdan, Raj K. ^{[5
]}

Kunos, George ^{[1
]}

机构：

[1] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA

[2] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA

[3] Univ Washington, Dept Biochem, Howard Hughes Med Inst, Seattle, WA 98195 USA

[4] British Columbia Canc Agcy, Terry Fox Labs, Vancouver, BC V5Z 4E6, Canada

[5] Organix Inc, Woburn, MA 01801 USA

来源：

NEUROPHARMACOLOGY | 2008年 / 54卷 / 01期

关键词：

anandamide; biosynthesis; N-arachidonoyl phosphatidylethanolamine; glycerophosphoarachidonoyl ethanolamide; phosphoanandamide;

D O I：

10.1016/j.neuropharm.2007.05.020

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Endocannabinoids, including anandamide (arachidonoyl ethanolamide) have been implicated in the regulation of a growing number of physiological and pathological processes. Anandamide can be generated from its membrane phospholipid precursor N-arachidonoyl phosphatidylethanolamine (NAPE) through hydrolysis by a phospholipase D (NAPE-PLD). Recent evidence indicates, however, the existence of two additional, parallel pathways. One involves the sequential deacylation of NAPE by alpha,beta-hydrolase 4 (Abhd4) and the subsequent cleavage of glycerophosphate to yield anandamide, and the other one proceeds through phospholipase C-mediated hydrolysis of NAPE to yield phosphoanandamide, which is then dephosphorylated by phosphatases, including the tyrosine phosphatase PTPN22 and the mositol 5' phosphatase SHIP1. Conversion of synthetic NAPE to AEA by brain homogenates from wild-type and NAPE-PLD-/- mice can proceed through both the PLC/phosphatase and Abdh4 pathways, with the former being dominant at shorter (< 10 min) and the latter at longer (60 min) incubations. In macrophages, the endotoxin-induced synthesis of anandamide proceeds uniquely through the phospholipase C/phosphatase pathway. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1 / 7

页数：7