2-AG

2-Arachidonoylglycerol (2-AG) is a monoglyceride of arachidonic acid and the quantitatively dominant endocannabinoid in the brain — present at concentrations roughly 200-fold higher than anandamide. It was independently identified as an endogenous cannabinoid receptor ligand by Mechoulam et al. (1995, Biochemical Pharmacology 50:83) in canine gut and by Sugiura et al. (1995, Biochemical and Biophysical Research Communications 215:89) in rat brain. Unlike AEA, 2-AG is a full agonist at both CB1 and CB2. Biosynthesis proceeds from membrane diacylglycerols via DAGLα (neurons) and DAGLβ (microglia, macrophages), triggered by postsynaptic depolarization or Gq-coupled receptor activation. Degradation is predominantly by MAGL (~85%), with smaller contributions from ABHD6 and ABHD12. 2-AG mediates classical short-term retrograde synaptic plasticity phenomena including DSI and DSE. → See also: MAGL, Retrograde signaling, CB1 receptor, Endocannabinoid.