RT Journal Article
SR Electronic
T1 Endocannabinoid Overload
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 993
OP 995
DO 10.1124/mol.110.069427
VO 78
IS 6
A1 Aron H. Lichtman
A1 Jacqueline L. Blankman
A1 Benjamin F. Cravatt
YR 2010
UL http://molpharm.aspetjournals.org/content/78/6/993.abstract
AB The signaling capacity of endogenous cannabinoids (“endocannabinoids”) is tightly regulated by degradative enzymes. This Perspective highlights a research article in this issue (p. 996) in which the authors show that genetic disruption of monoacylglycerol lipase (MAGL), the principal degradative enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG), causes marked elevations in 2-AG levels that lead to desensitization of brain cannabinoid receptors. These findings highlight the central role that MAGL plays in endocannabinoid metabolism in vivo and reveal that excessive 2-AG signaling can lead to functional antagonism of the brain cannabinoid system.