Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus

被引：181

作者：

Makara, JK

Mor, M

Fegley, D

Szabó, SI

Kathuria, S

Astarita, G

Duranti, A

Tontini, A

Tarzia, G

Rivara, S

Freund, TF

Piomelli, D ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA

[2] Univ Urbino, Inst Med Chem, I-61029 Urbino, Italy

[3] Hungarian Acad Sci, Inst Expt Med, H-1083 Budapest, Hungary

[4] Univ Parma, Dept Pharmaceut, I-43100 Parma, Italy

[5] Univ Calif Irvine, Ctr Drug Discovery, Irvine, CA 92697 USA

来源：

NATURE NEUROSCIENCE | 2005年 / 8卷 / 09期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nn1521

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The functions of 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid found in the brain, remain largely unknown. Here we show that two previously unknown inhibitors of monoacylglycerol lipase, a presynaptic enzyme that hydrolyzes 2-AG, increase 2-AG levels and enhance retrograde signaling from pyramidal neurons to GABAergic terminals in the hippocampus. These results establish a role for 2-AG in synaptic plasticity and point to monoacylglycerol lipase as a possible drug target.

引用

收藏

页码：1139 / 1141

页数：3

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