Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum

被引：249

作者：

Maccarrone, Mauro ^{[1
,2
]}

Rossi, Silvia ^{[2
,3
]}

Bari, Monica ^{[4
]}

De Chiara, Valentina ^{[2
,3
]}

Fezza, Filomena ^{[2
,4
]}

Musella, Alessandra ^{[2
,3
]}

Gasperi, Valeria ^{[1
]}

Prosperetti, Chiara ^{[2
,3
]}

Bernardi, Giorgio ^{[2
,3
]}

Finazzi-Agro, Alessandro ^{[4
]}

Cravatt, Benjamin F. ^{[3
,5
,6
]}

Centonze, Diego ^{[2
,3
]}

机构：

[1] Univ Teramo, Dipartimento Sci Biomed, I-64100 Teramo, Italy

[2] CERC, Fdn Santa Lucia, I-00143 Rome, Italy

[3] Univ Roma Tor Vergata, Dipartimento Neurosci, Neurol Clin, I-00133 Rome, Italy

[4] Univ Roma Tor Vergata, Dipartimento Med Sperimentale & Sci Biochim, I-00133 Rome, Italy

[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[6] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA

来源：

NATURE NEUROSCIENCE | 2008年 / 11卷 / 02期

关键词：

D O I：

10.1038/nn2042

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Of the endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have received the most study. A functional interaction between these molecules has never been described. Using mouse brain slices, we found that stimulation of metabotropic glutamate 5 receptors by 3,5-dihydroxyphenylglycine (DHPG) depressed inhibitory transmission in the striatum through selective involvement of 2-AG metabolism and stimulation of presynaptic CB1 receptors. Elevation of AEA concentrations by pharmacological or genetic inhibition of AEA degradation reduced the levels, metabolism and physiological effects of 2-AG. Exogenous AEA and the stable AEA analog methanandamide inhibited basal and DHPG-stimulated 2-AG production, confirming that AEA is responsible for the downregulation of the other eCB. AEA is an endovanilloid substance, and the stimulation of transient receptor potential vanilloid 1 (TRPV1) channels mimicked the effects of endogenous AEA on 2-AG metabolism through a previously unknown glutathione-dependent pathway. Consistently, the interaction between AEA and 2-AG was lost after pharmacological and genetic inactivation of TRPV1 channels.

引用

页码：152 / 159

页数：8

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