2-Arachidonoylglycerol

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ImageFile = 2ag.svg
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IUPACName = 1,3-Dihydroxy-2-propanyl (5Z,8Z,11Z,14Z)-5,8,11,14-icosatetraenoate
OtherNames = 2-AG, 2-arachidonoylglycerol
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CASNo = 53847-30-6
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Formula = C₂₃H₃₈O₄
MolarMass = 378.3 g/mol
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2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor.Stella, N., Schweitzer, P., Piomelli, D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388 773-778 (1997).] 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).] 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 mouse and rat brain (~5-10 nmol/g tissue).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). ] Formation of 2-AG is calcium-dependent and is mediated by the activities of phospholipase C (PLC) and diacylglycerol lipase (DAGL). 2-AG acts as a full agonist at the CB1 receptor.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).] 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-AG is hydrolyzed "in vitro" by monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and the uncharacterized serine hydrolase enzymes ABHD6 and ABHD12. [Blankman J.L. et al., "A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol." Chem. Biol. 2007 Dec;14(12):1347-56 PMID 18096503 ] The exact contribution of each of these enzymes to the termination of 2-AG signaling "in vivo" is unknown, though it is estimated that MAGL is responsible for ~85% of this activity. 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 maternal bovine and human milk. [cite journal | author = Fride E, Bregman T, Kirkham TC.
year = 2005
month = April
title = Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood.
journal = Experimental Biology and Medicine
volume = 230
issue = 4
pages = 225–234
doi = 10.1371/journal.pbio.0020286
pmid = 15792943
url = http://www.ebmonline.org/cgi/reprint/230/4/225.pdf | format = | accessdate = ]

References

Footnotes

General references

*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).