2-arachidonyl-glycerol

A different type of endocannabinoid that is also an arachidonic acid derivative was first isolated from canine gut and identified as 2-arachidonyl glycerol (2-AG) (Fig. 3) (Mechoulam, 1995a). 

With the discovery of anandamide and 2-arachidonyl glycerol as two new families of endocannabinoids, cannabinoid research has taken major... 

Di Marzo V. 2-Arachidonyl-glycerol as an endocannabinoid limelight for a formerly neglected metabolite. Biochem (Moscow) 1998 63 13-21. 

Hydrolysis of 1P3 from membrane lipids yields l-acyl-2-arachidonyl-glycerol, which remains in the piasma membrane. The arachidonate esterified at the 2-po-sition may be hydrolyzed by phospholipase Aj, to yield free arachidonate. The pathway leading to the release of IP3 and arachidonate is show o in Figure 9.98, The events depicted occur in a burst. They occur mainly within a time frame of a minute or so of stimuiation of the cell, Stimulation of the cell can induce an increase in the concentration of free arachidonic acid in the cell. This arachidonate car be used by cyclooxygenase, Cyclooxygenase is a membrane-bound enzyme of the endoplasmic reticulum. The active site faces the cytoplasm. The enzyme Is bifunchonal. It catalyzes the attachment of oxygen moiecuies to arachidonic acid,... 

FIGURE 9.98 Events taking place in the plasma membrane on stimulation of a cell. Phospha tidylinositol (Pi) and more hi ly phosphoiylated versions of this lipid account for 2 to 8% of the lipids of the plasma membrane of eukaryotic cdIs. The inositol 1,4,5 triphosphate (fP3) moiety of phosphatidyl inositol- 4,8-di phosphate may be hydiulyitec from this lipid immediately after the cell is stimulated. For example, the stimulation of platelets by thrombin or the islets of the pancreas by glucose is followed by the release of 1P3 into the cytoplasm. In some cells, arachidonic acid is hydrolyzed from l-acyl-2-arachidonyl-glyceroL which can Support a burst of prostaglandin. synthesis. 

Gonsiorek W, Lunn C, Fan X, Narula S, Lundell D, Hipkin RW (2000) Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor antagonism by anandamide. Mol Pharmacol 57 1045-1050... 

Lee M, Yang KH, Kaminski NE (1995) Effects of putative cannabinoid receptor ligands, anandamide and 2-arachidonyl-glycerol, on immune function in B6C3F1 mouse splenocytes. J Pharmacol Exp Ther 275 529-536... 

Stefano GB, Bilfinger TV, Rialas CM, Deutsch DG (2000) 2-Arachidonyl-glycerol stimulates nitric oxide release from human immune and vascular tissues and invertebrate immunocytes by cannabinoid receptor 1. Pharmacol Res 42 317-322... 

Ben-Shabat, S., Pride, E., Sheskin, T., Tamiri, T., Rhee, M.EI., 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-arachidonyl-glycerol cannabinoid activity. Eur. J. Pharmacol., 353 23-31. 

Goparaju SK, Ueda N, Yanaguchi H, and Yamamoto S (1998) Anandamide amidohydrolase reacting with 2-arachidonyl glycerol, another cannabinoid receptor ligand. FEES Lett 422 69-73. 

FIGURE 3.4 Effect of endocannabinoids on AMPA glutamate receptor. In Xenopus oocytes expressing the recombinant rat GluIT3 subunit of AMPA receptor, anandamide, 2-arachidonyl glycerol, and noladin ether inhibited kainate-activated currents. The order of potency of the endocannabinoids in inhibiting receptor currents in oocytes was anandamide > 2-arachidonyl glycerol > noladin ether. 

Ouyang, Y, Hwang, S.G., Han, S.H., and Kaminski, N.E. (1998) Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl-glycerol is mediated through down-regulation of the nuclear factor of activated T cells, Molecular Pharmacology 53 676-683. 

FIGURE 8.1 The principal endogenous cannabinoids. Anandamide and 2-arachidonyl glycerol (2-AG) are the most well-studied endocannabinoids however, conjugates with other fatty acids such as palmitic and eicosapenteneoic acid are well known. Novel structures such as virodhamine and noladin ether have also been reported. Arachidonic acid derivatives with other molecules such as dopamine (NADA) and glycine (NAGly) are also known. 

Hanus, L., Alu-Lafi, S., Fride, E., Breuer, A., Vogel, Z., Shalev, D.E., Kustanovich, 1., and Mechoulam, R. (2001) 2-Arachidonyl glycerol ether, an endogenous agonist of the cannabinoid GBj receptor, Proc. Natl. Acad. Sci. USA9S-. 3662-3665. 

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