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

  title={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},
  author={Sachiko Kondo and Hirobumi Kondo and Shinji Nakane and Tomoko Kodaka and Akira Tokumura and Keizo Waku and Takayuki Sugiura},
  journal={FEBS Letters},

Generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain.

Ex vivo 2-arachidonoylglycerol produced during neural excitation may play a regulatory role in calming the enhanced synaptic transmission and is known to depress neurotransmission and to exert anticonvulsant activities.

Evidence for the Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in 12-O-Tetradecanoylphorbol-13-acetate-induced Acute Inflammation in Mouse Ear*

It is found that the amount of 2-arachidonoylglycerol was markedly augmented in inflamed mouse ear, suggesting that the CB2 receptor is involved in the swelling.

Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor

2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules, and anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively.

Depolarization-induced rapid generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in rat brain synaptosomes.

Results strongly suggest that the endogenous ligand for the cannabinoid receptors, 2-AG, generated through increased phospholipid metabolism upon depolarization, plays an important role in attenuating glutamate release from the synaptic terminals by acting on the CB1 receptor.

2-Arachidonoylglycerol Induces the Migration of HL-60 Cells Differentiated into Macrophage-like Cells and Human Peripheral Blood Monocytes through the Cannabinoid CB2 Receptor-dependent Mechanism*

The results strongly suggest that 2-arachidonoylglycerol induces the migration of several types of leukocytes such as macrophages/monocytes through a CB2 receptor-dependent mechanism thereby stimulating inflammatory reactions and immune responses.

Regulation of inflammation by cannabinoids, the endocannabinoids 2‐arachidonoyl‐glycerol and arachidonoyl‐ethanolamide, and their metabolites

2‐Arachidonoyl‐glycerol (2‐AG) and arachidonyl‐ethanolamide (AEA) are endocannabinoids that have been implicated in many physiologic disorders, including obesity, metabolic syndromes, hepatic



Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells.

The results suggest that the Ca2+-induced formation of 2-AG proceeds through the intermediacy of AcAGs but not necessarily through phospholipase C activation, and supports the hypothesis that this cannabimimetic monoacylglycerol might be a physiological neuromodulator.

Isotope Dilution Mass Spectrometric Measurements Indicate That Arachidonylethanolamide, the Proposed Endogenous Ligand of the Cannabinoid Receptor, Accumulates in Rat Brain Tissue Post Mortem but Is Contained at Low Levels in or Is Absent from Fresh Tissue*

The findings indicate that the AEA content of fresh rat brain and of NAPE precursors from which AEA might be derived are exceedingly low and that AEA can be produced artifactually from biological materials.

Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine.

Several lines of evidence strongly suggest that the second pathway, rather than the first one, meets the requirements and conditions for the synthesis of various species of N-acylethanolamine including anandamide in the brain.

Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108-15 cells.

The results suggest that the structure of 2-arachidonoylglycerol is strictly recognized by theCB1 receptor, which raises the possibility that the CB1 receptor is originally a 2-Arachidonoyslglycersol receptor.

Ca2+ ‐Dependent Release from Rat Brain of Cannabinoid Receptor Binding Activity

It is demonstrated here that the Ca2+ ionophore A23187 can induce release of cannabinoid‐like binding activity in the presence but not in the absence of Ca2+.

Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand, through N-acylphosphatidylethanolamine pathway in testis: involvement of Ca(2+)-dependent transacylase and phosphodiesterase activities.

It is confirmed that testis microsomes contain a phosphodiesterase activity catalyzing the release of anandamide from N-arachidonoylPE, and the N-acylPE pathway is important in the synthesis of an andamide in this tissue.

Occurrence and Biosynthesis of Endogenous Cannabinoid Precursor,N-Arachidonoyl Phosphatidylethanolamine, in Rat Brain

The results demonstrate, therefore, that rat brain tissue contains the complement of enzymatic activity and lipid substrates necessary for the biosynthesis of the anandamide precursor N-arachidonoyl PE, and suggest that biosynthesis and formation of an andamide are tightly coupled processes, which may be stimulated by elevations in intracellular Ca2+ occurring during neural activity.

Enzymatic synthesis of anandamide, an endogenous ligand for the cannabinoid receptor, by brain membranes.

  • W. DevaneJ. Axelrod
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
The ability of brain tissue to enzymatically synthesize anandamide and the existence of specific receptors for this eicosanoid suggest the presence of an andamide-containing (anandaergic) neurons.

Formation and inactivation of endogenous cannabinoid anandamide in central neurons

It is reported that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents, indicating that multiple biochemical pathways may participate in an andamide formation in brain tissue.