2-Arachidonoylglycerol

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2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor.^[1]^[2] It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. Unlike anandamide, 2-AG is present at relatively high levels in the central nervous system; it is the most abundant molecular species of monoacylglycerol found in rat brain.^[2]^[3] Formation of 2-AG is calcium-dependent and is mediated by the activities of phospholipase C (PLC) and diacylglycerol lipase (DAG).^[2] 2-AG acts as a full agonist at the CB1 receptor.^[4] At a concentration of 0.3 nM, 2-AG induces a rapid, transient increase in intracellular free calcium in NG108-15 neuroblastoma X glioma cells through a CB1 receptor-dependent mechanism.^[2] 2-AG is metabolized in vitro by monoacylglycerol lipase (MGL) and fatty acid amide hydrolase, with MGL likely being the principle metabolizing enzyme in vivo.^[4]

[edit] References

^ Stella, N., Schweitzer, P., Piomelli, D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388 773-778 (1997).
^ ^a ^b ^c ^d Sugiura, T., Kodaka, T., Nakane, S., et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J Biol Chem 274 2794-2801 (1999).
^ Kondo, S., Kondo, H., Nakane, S., et al. 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: Identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through Ca2+-dependent and -independent mechanisms. FEBS Lett 429 152-156 (1998).
^ ^a ^b Savinainen, J. R., Jarvinen, T., Laine, K. and Laitinen, J. T. Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar membranes. Br. J. Pharmacol. 134, 664–672(2001).

Dinh, T.P., Carpenter, D., Leslie, F.M., et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99(16) 10819-10824 (2002).