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2-Arachidonoyl glycerol (2-AG) is an endogenous agonist of the CB1 receptor.1,2 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.1,3 Formation of 2-AG is calcium-dependent and is mediated by the activities of PLC and DAG lipase.1 2-AG acts as a full agonist at the CB1 receptor. 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 MAG lipase and fatty acid amide hydrolase, with MAG lipase likely being the principle metabolizing enzyme in vivo.4
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1
Stella, N., Schweitzer, P., Piomelli, D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388 773-778 (1997).
2
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).
3
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).
4
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).
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