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| Names | |
|---|---|
| IUPAC name 2-O-[(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoyl]glycerol | |
| Systematic IUPAC name 1,3-Dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate | |
| Other names 2-AG, 2-arachidonoylglycerol | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
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| UNII | |
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| Properties | |
| C23H38O4 | |
| Molar mass | 378.3 g/mol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
2-Arachidonoylglycerol (2-AG) is anendocannabinoid, anendogenousagonist of theCB1 receptor and the primary endogenous ligand for the CB2 receptor.[1][2] It is anester formed from theomega-6 fatty acidarachidonic acid andglycerol. It is present at relatively high levels in the central nervous system, with cannabinoid neuromodulatory effects. It has been found in bovine andhuman milk.[3] The chemical was first described in 1994–1995, although it had been discovered some time before that. The activities ofphospholipase C (PLC) anddiacylglycerol lipase (DAGL) mediate its formation.[4] 2-AG issynthesized fromarachidonic acid-containingdiacylglycerol (DAG).
2-AG, unlikeanandamide (anotherendocannabinoid), is present at relatively high levels in the central nervous system; it is the most abundant molecular species of monoacylglycerol found in mouse and rat brain (~5–10 nmol/g tissue).[2][5] Detection of 2-AG in brain tissue is complicated by the relative ease of its isomerization to 1-AG during standard lipid extraction conditions. It has been found in bovine as well as human milk.[6][7][8]
2-AG was discovered byRaphael Mechoulam and his student Shimon Ben-Shabat.[9] 2-AG was a known chemical compound but its occurrence in mammals and its affinity for the cannabinoid receptors were first described in 1994–1995. A research group atTeikyo University reported the affinity of 2-AG for the cannabinoid receptors in 1994–1995,[10][11] but the isolation of 2-AG in the canine gut was first reported in 1995 by the research group ofRaphael Mechoulam at theHebrew University of Jerusalem, which additionally characterized its pharmacological propertiesin vivo.[12] 2-Arachidonoylglycerol, next withAnandamide, was the secondendocannabinoid discovered. The cannabinoid established the existence of a cannabinoid neuromodulatory system in thenervous system.[13]
Unlikeanandamide, formation of 2-AG is calcium-dependent and is mediated by the activities ofphospholipase C (PLC) anddiacylglycerol lipase (DAGL).[2] 2-AG acts as a full agonist at the CB1 receptor.[14] At a concentration of 0.3 nM, 2-AG induces a rapid, transient increase in intracellular free calcium inNG108-15neuroblastoma X glioma cells through a CB1 receptor-dependent mechanism.[2] 2-AG is hydrolyzedin vitro bymonoacylglycerol lipase (MAGL),fatty acid amide hydrolase (FAAH), and the uncharacterizedserine hydrolase enzymesABHD2,[15]ABHD6 andABHD12.[16] The exact contribution of each of these enzymes to the termination of 2-AG signalingin vivo is unknown, though it is estimated that MAGL is responsible for ~85% of this activity in the brain.[17] There have been identifiedtransport proteins for 2-arachidonoylglycerol and anandamide. These include theheat shock proteins (Hsp70s) andfatty acid binding proteins (FABPs).[18][19]
2-Arachidonoylglycerol issynthesized fromarachidonic acid-containingdiacylglycerol (DAG), which is derived from the increase ofinositol phospholipid metabolism by the action ofdiacylglycerol lipase. The molecule can also be formed from pathways like thehydrolysis derived (bydiglyceride) from bothphosphatidylcholine (PC) andphosphatidic acid (PAs) by the action of DAG lipase and the hydrolysis of arachidonic acid-containinglysophosphatidic acid by the action of aphosphatase.[20]
