| http://purl.uniprot.org/citations/20855465 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20855465 | http://www.w3.org/2000/01/rdf-schema#comment | "Endocannabinoids are lipid molecules that serve as natural ligands for the cannabinoid receptors CB1 and CB2. They modulate a diverse set of physiological processes such as pain, cognition, appetite, and emotional states, and their levels and functions are tightly regulated by enzymatic biosynthesis and degradation. 2-Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid in the brain and is believed to be hydrolyzed primarily by the serine hydrolase monoacylglycerol lipase (MAGL). Although 2-AG binds and activates cannabinoid receptors in vitro, when administered in vivo, it induces only transient cannabimimetic effects as a result of its rapid catabolism. Here we show using a mouse model with a targeted disruption of the MAGL gene that MAGL is the major modulator of 2-AG hydrolysis in vivo. Mice lacking MAGL exhibit dramatically reduced 2-AG hydrolase activity and highly elevated 2-AG levels in the nervous system. A lack of MAGL activity and subsequent long-term elevation of 2-AG levels lead to desensitization of brain CB1 receptors with a significant reduction of cannabimimetic effects of CB1 agonists. Also consistent with CB1 desensitization, MAGL-deficient mice do not show alterations in neuropathic and inflammatory pain sensitivity. These findings provide the first genetic in vivo evidence that MAGL is the major regulator of 2-AG levels and signaling and reveal a pivotal role for 2-AG in modulating CB1 receptor sensitization and endocannabinoid tone."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.110.068304"xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Gao Y."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Lu P."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Kennedy J.D."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Pangalos M.N."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Zhang M.Y."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Chanda P.K."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Bates B."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Mark L."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Samad T.A."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Garbe D."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Strassle B.W."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Kouranova E.V."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Piesla M.J."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Ring R.H."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Whiteside G.T."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Bingham B."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Kowal D."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Btesh J."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/author | "Uveges A."xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/name | "Mol Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/20855465 | http://purl.uniprot.org/core/pages | "996-1003"xsd:string |