2-Arachidonoyl-glycerol

Endocannabinoids are endogenous mediators acting via the binding to, and activation of, cannabinoid receptors, CBX and CB2 [1]. iV-arachidonoy 1-ethanol-amine (AEA, anandamide) and 2-arachidonoyl-glycerol (2-AG) (Fig. 1) are the two most studied endocannabinoids. In the nervous system, endocannabinoids act as... 

Melis, M., Perra, S., Muntoni, A.L., Pillolla, G., Lutz, B., Marsicano, G., Di Marzo, V., Gessa, G.L., and Pistis, M., Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons, J. Neurosci., 24, 10707, 2004. 

Endocannabinoids are endogenous ligands for the CB1 receptor. The best established are anandamide (N-arachidonoylethanolamine) and 2-AG (2-arachidonoyl-glycerol). Others may also exist. Pathways involved in the formation and inactivation of anandamide and 2-AG are shown in Figure 56-6. Some steps in their formation are Ca2+-dependent. This explains the ability of neuronal depolarization, which increases postsynaptic intracellular Ca2+ levels, to stimulate endocannabinoid formation and release. Some neurotransmitter receptors (e.g. the D2 dopamine receptor) also stimulate endocannabinoid formation, probably by modulating postsynaptic Ca2+ levels or signaling pathways (e.g. PLC) that regulate endocannabinoid formation. 

Di Marzo V. (1998). 2-Arachidonoyl-glycerol as an "endocannabinoid" limelight for a formerly neglected metabolite. Biochemistry (Moscow). 63(1) 13-21. 

Later, we described the isolation of a second type of cannabinoid receptor ligand, 2-arachidonoyl glycerol (2-AG) (K = 5-85 0.12 xM), an ester isolated from canine gut. " This was the first putative endogenous cannabinoid receptor ligand isolated from a peripheral tissue. Later, Sugiura et al isolated independently this compound from brain. 

T, De PetroceUis L, Di Marzo V, Mechoulam R, An entourage effect Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabi-noid activity, Eur J Pharmacol 353 23—31, 1998. 

The endogenous cannabinoid 2-arachidonoyl-glycerol is thought to play important roles both in the brain (Chapter 30) and in the immune system (Chapter 31). Leukocyte 12-oxygenase acts on this compound.360 What products would be expected ... 

THE BRAIN S OWN MARIJUANA-LIKE NEUROTRANSMITTER The very high potency and structure of the cannabinoids contained within the marijuana plant enable them to cross the blood—brain barrier and bind to a receptor for the brain s very own endogenous cannabinoid neurotransmitter system. If this were not true, then the marijuana plant would be popular only for its use in making rope, paper, and cloth. The two currently identified neurotransmitters compounds (and there are probably more) in this system are anandamide, from the Sanskrit word amnia () meaning bliss, and 2-AG (2-arachidonoyl-glycerol). Unlike the other neurotransmitters that I ve discussed, these two endocannabinoids are not stored in synaptic vesicles. 

Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M. H., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V., and Mechoulam, R. (1998). An entourage effect Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur. 

Walter L, Franklin A, Witting A, MoUer T, SteUa N (2002) Astrocytes in culture produce anandamide and other acylethanolamides. J Biol Chem 277 20869-20876 Walter L, SteUa N (2003) EndotheUn-1 increases 2-arachidonoyl glycerol (2-AG) production in astrocytes. GUa 44 85-90... 

AA arachidonic acid, 2-AG 2-arachidonoyl glycerol, DHA docosahexaenoic add, FAAH fatty add amide hydrolase, DAGL sn-1-selective diacylglycerol lipase, MAGL monoacylglycerol lipase, NAPE-PLD N-acylphosphatidylethanolamine-selective phospholipase D... 

Di Marzo V, De Petrocellis L, Sugiura T, Waku K (1996) Potential biosynthetic connections between the two cannabimimetic eicosanoids, anandamide and 2-arachidonoyl-glycerol, in mouse neuroblastoma cells. Biochem Biophys Res Commun 227 281-288... 

Hajos N, Kathuria S, Dinh T, Piomelh D, Freund TF (2004) Endocannabinoid transport tightly controls 2-arachidonoyl glycerol actions in the hippocampus effects of low temperature and the transport inhibitor AM404. Eur J Neurosci 19 2991-2996... 

Kunos G (2000) Cardiovascular effects of 2-arachidonoyl glycerol in anesthetized mice. Hypertension... 

Saario SM, Salo OM, Nevalainen T, Poso A, Laitinen JT, Jarvinen T, Niemi R (2005) Characterization of the sulfhydryl-sensitive site in the enzyme responsible for hydrolysis of 2-arachidonoyl-glycerol in rat cerebellar membranes. Chem Biol 12 649—656... 

Members of the eicosanoid group of cannabinoid receptor agonists have markedly different structures both from the aminoalkylindoles and from classical and nonclassical cannabinoids. Important members of this group are the endocannabinoids, arachidonoylethanolamide (anandamide), 0-arachidonoylethan-olamine (virodhamine), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl... 

Several cannabinoid receptor agonists bind more or less equally well to CBi and CB2 receptors (Table 2), although they do exhibit different relative intrinsic activities at these receptors. Among these are HU-210, CP55940, lt-(-i-)-WlN55212, (-)-A -THC, anandamide and 2-arachidonoyl glycerol (reviewed in Howlett et al. 2002 Pertwee 1999a). 

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