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Cited by 172

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells

Open access
Muccioli, Giulio G., Xu, Cong, Odah, Emma, Cudaback, Eiron, Cisneros, Jose Antonio, Lambert, Didier M., López Rodríguez, María Luz, Bajjalieh, Sandra, Stella, Nephi·2007·The Journal of Neuroscience

Abstract

The endocannabinoids (eCBs) anandamide and 2-arachidonoyl glycerol (2-AG) are inactivated by a two-step mechanism. First, they are carried into cells, and then anandamide is hydrolyzed by fatty acid amide hydrolase (FAAH) and 2-AG by monoacylglycerol lipase (MGL). Here we provide evidence for a previously undescribed MGL activity expressed by microglial cells. We found that the mouse microglial cell line BV-2 does not express MGL mRNA and yet efficiently hydrolyzes 2-AG. URB597 (3′-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) reduces this hydrolysis by 50%, suggesting the involvement of FAAH. The remaining activity is blocked by classic MGL inhibitors [[1,1-biphenyl]-3-yl-carbamic acid, cyclohexyl ester (URB602) and MAFP (methylarachidonyl fluorophosphate)] and is unaffected by inhibitors of COXs (cyclooxygenases), LOXs (lipooxygenases), and DGLs (diacylglycerol lipases), indicating the involvement of a novel MGL activity. Accordingly, URB602 leads to selective accumulation of 2-AG in intact BV-2 cells. Although MGL expressed in neurons is equally distributed between the cytosolic, mitochondrial, and nuclear fractions, the novel MGL activity expressed by BV-2 cells is enriched in mitochondrial and nuclear fractions. A screen for novel inhibitors of eCB hydrolysis identified several compounds that differentially block MGL, FAAH, and the novel MGL activity. Finally, we provide evidence for expression of the novel MGL by mouse primary microglia in culture. Our results suggest the presence of a novel, pharmacologically distinct, MGL activity that controls 2-AG levels in microglia.

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Crossref · 10.1523/jneurosci.4830-06.2007

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Metadata

Authors
Muccioli, G. G., Xu, C., Odah, E., Cudaback, E., Cisneros, J. A., Lambert, D. M., López Rodríguez, M. L., Bajjalieh, S., & Stella, N.
Venue
The Journal of Neuroscience
Published
2007-03-14
Volume
27
Issue
11
Pages
2883-2889
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2005310692
Cited by
172
References
7
FWCI
14.10
Type
journal article
Language
en
Open access
hybrid

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Muccioli, G. G., Xu, C., Odah, E., Cudaback, E., Cisneros, J. A., Lambert, D. M., López Rodríguez, M. L., Bajjalieh, S., & Stella, N. (2007). Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.4830-06.2007

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