Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand

Prog Lipid Res. 2006 Sep;45(5):405-46. doi: 10.1016/j.plipres.2006.03.003. Epub 2006 Apr 19.

Abstract

2-Arachidonoylglycerol (2-AG) is a unique molecular species of monoacylglycerol isolated in 1995 from rat brain and canine gut as an endogenous ligand for the cannabinoid receptors. 2-AG is rapidly formed from arachidonic acid-containing phospholipids through increased phospholipid metabolism, such as enhanced inositol phospholipid turnover, in various tissues and cells upon stimulation. 2-AG binds to the cannabinoid receptors (CB1 and CB2) and exhibits a variety of cannabimimetic activities in vitro and in vivo. Notably, anandamide, another endogenous ligand for the cannabinoid receptors, often acts as a partial agonist at these cannabinoid receptors, whereas 2-AG acts as a full agonist in most cases. The results of structure-activity relationship studies suggested that 2-AG rather than anandamide is the true natural ligand for both the CB1 and the CB2 receptors. Evidence is gradually accumulating which shows that 2-AG plays physiologically essential roles in diverse biological systems. For example, several lines of evidence indicate that 2-AG plays an important role as a retrograde messenger molecule in the regulation of synaptic transmission. 2-AG has also been shown to be involved in the regulation of various types of inflammatory reactions and immune responses. In this review, we focused on 2-AG, and summarized information concerning its biosynthesis, metabolism, bioactions and physiological significance, including our latest experimental results.

Publication types

  • Review

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology
  • Arachidonic Acids / physiology*
  • Biological Transport / physiology
  • Endocannabinoids
  • Glycerides / metabolism
  • Glycerides / pharmacology
  • Glycerides / physiology*
  • Humans
  • Immune System / physiology
  • Ligands
  • Mice
  • Nervous System Physiological Phenomena
  • Neurotransmitter Agents / physiology
  • Oxidation-Reduction
  • Rats
  • Receptors, Cannabinoid / metabolism*
  • Structure-Activity Relationship
  • Synaptic Transmission / physiology

Substances

  • Arachidonic Acids
  • Endocannabinoids
  • Glycerides
  • Ligands
  • Neurotransmitter Agents
  • Receptors, Cannabinoid
  • glyceryl 2-arachidonate