The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-08

AUTHORS

William R Marrs, Jacqueline L Blankman, Eric A Horne, Aurore Thomazeau, Yi Hsing Lin, Jonathan Coy, Agnes L Bodor, Giulio G Muccioli, Sherry Shu-Jung Hu, Grace Woodruff, Susan Fung, Mathieu Lafourcade, Jessica P Alexander, Jonathan Z Long, Weiwei Li, Cong Xu, Thomas Möller, Ken Mackie, Olivier J Manzoni, Benjamin F Cravatt, Nephi Stella

ABSTRACT

The endocannabinoid 2-arachidonoylglycerol (2-AG) regulates neurotransmission and neuroinflammation by activating CB1 cannabinoid receptors on neurons and CB2 cannabinoid receptors on microglia. Enzymes that hydrolyze 2-AG, such as monoacylglycerol lipase, regulate the accumulation and efficacy of 2-AG at cannabinoid receptors. We found that the recently described serine hydrolase alpha-beta-hydrolase domain 6 (ABHD6) also controls the accumulation and efficacy of 2-AG at cannabinoid receptors. In cells from the BV-2 microglia cell line, ABHD6 knockdown reduced hydrolysis of 2-AG and increased the efficacy with which 2-AG can stimulate CB2-mediated cell migration. ABHD6 was expressed by neurons in primary culture and its inhibition led to activity-dependent accumulation of 2-AG. In adult mouse cortex, ABHD6 was located postsynaptically and its selective inhibition allowed the induction of CB1-dependent long-term depression by otherwise subthreshold stimulation. Our results indicate that ABHD6 is a rate-limiting step of 2-AG signaling and is therefore a bona fide member of the endocannabinoid signaling system. More... »

PAGES

951

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nn.2601

DOI

http://dx.doi.org/10.1038/nn.2601

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025157163

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20657592


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479 rdf:type schema:Organization
480 https://www.grid.ac/institutes/grid.7942.8 schema:alternateName Université Catholique de Louvain
481 schema:name Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, CHAM7230, Louvain Drug Research Institute, Université catholique de Louvain, Bruxelles, Belgium.
482 rdf:type schema:Organization
 




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