Disease relevance of C13856

• In the reserpine-treated rat, an animal model of Parkinson's disease, suppression of locomotion is accompanied by a sevenfold increase in the levels of the 2AG in the globus pallidus, but not in the other five brain regions analyzed [1].
• The possible involvement of 2-arachidonoylglycerol (2-AG), an endogenous ligand for the cannabinoid receptors (CB1 and CB2), in contact dermatitis in mouse ear was investigated [2].
• Other endocannabinoids such as anandamide, 2-arachidonoylglycerol, and noladin ether did not show inhibitory activity in the HIV-1 replication assays [3].
• The migration induced by 2-arachidonoylglycerol was blocked by treatment of the cells with either SR144528, a CB2 receptor antagonist, or pertussis toxin, suggesting that the CB2 receptor and Gi/Go are involved in the 2-arachidonoylglycerol-induced migration [4].
• We reported earlier that closed head injury (CHI) in mice causes a sharp elevation of brain 2-arachidonoylglycerol (2-AG) levels, and that exogenous 2-AG reduces brain edema, infarct volume and hippocampal death and improved clinical recovery after CHI [5].

Psychiatry related information on C13856

• Food deprivation for 24 h was accompanied by a significant increase of anandamide, but not 2-arachidonoylglycerol, levels only in the telencephalon [6].
• 3. We observed that, in the limbic forebrain, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) contents increased after 7 days of alcoholization, then to dramatically decrease after 48 h of alcohol deprivation and, in the case of 2-AG, to further decrease when rats were allowed to relapse to alcohol consumption [7].

High impact information on C13856

• P2X7 receptors control 2-arachidonoylglycerol production by microglial cells [8].
• There are no age-dependent differences in the tissue levels of the endocannabinoids anandamide and 2-arachidonoylglycerol or the density of CB1 in the hypothalamus, limbic forebrain, amygdala, and cerebellum [9].
• Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors able to mimic several pharmacological effects of Delta-9-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana [10].
• Here we report the presence in two regions of the basal ganglia, the globus pallidus and substantia nigra, of the endocannabinoids 2-arachidonoylglycerol (2AG) and anandamide [1].
• Upon stimulation with either of the CB2 ligands JWH015 and 2-arachidonoylglycerol (2-AG), neutrophil-like HL60 cells rapidly extended and retracted one or more pseudopods containing F-actin in different directions instead of developing front/rear polarity typically exhibited by migrating leukocytes [11].

Chemical compound and disease context of C13856

• Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in Oxazolone-Induced Contact Dermatitis in Mice [2].
• Intraluminal administration of the endocannabinoids N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) causes inflammation similar to that caused by Clostridium difficile toxin A in the rat ileum [12].
• Perfusion with either palmitoylethanolamide or 2-arachidonoylglycerol 15 min before and throughout the ischemia mimicked preconditioning inasmuch as it protected the endothelium in a similar fashion [13].
• These results suggest that effectiveness of direct hemoperfusion through immobilized polymyxin B fibers in endotoxemia involves elimination of 2-arachidonoylglycerol action [14].
• On the day after the operation, lipopolysaccharide (Escherichia coli, O111:B4; 1 mg/kg) or 2-arachidonoylglycerol (1 mg/kg) was given intraperitoneally (i.p.) and direct hemoperfusion through immobilized polymyxin B fibers was carried out for 2 h [14].

Biological context of C13856

• Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds [15].
• The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) is produced by neurons and other cells in a stimulus-dependent manner and undergoes rapid biological inactivation through transport into cells and catalytic hydrolysis [16].
• RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol [16].
• Cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoylglycerol have been suggested to regulate food intake in several animal phyla [6].
• Several cannabimimetic molecules as well as Delta(9)-tetrahydrocannabinol are known to depress neurotransmission and to exert anticonvulsant activities; endogenous 2-arachidonoylglycerol produced during neural excitation may play a regulatory role in calming the enhanced synaptic transmission [17].

Anatomical context of C13856

• In this study, we examined the effects of 2-arachidonoylglycerol on the motility of HL-60 cells differentiated into macrophage-like cells [4].
• The 2-arachidonoylglycerol-induced migration was also observed for two other types of macrophage-like cells, the U937 cells and THP-1 cells, as well as human peripheral blood monocytes [4].
• These results strongly suggest that the CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic natural ligand for the CB2 receptor that is abundant in the immune system [18].
• Using the human Raji B cell line as a model, we demonstrate in a transwell assay that moderate migration occurs upon stimulation of the CB2 receptor with the endocannabinoid 2-arachidonoylglycerol, which is enhanced by CD40 costimulation [19].
• All tumoral samples had higher contents of anandamide and 2-arachidonoylglycerol compared with the normal hypophysis [20].

Associations of C13856 with other chemical compounds

• Activities of HU-210 and CP55940, potent cannabinoid receptor agonists, were also detectable from as low as 0.3 nM, whereas the maximal responses induced by these compounds were low compared with 2-arachidonoylglycerol [15].
• The cortex and hippocampus of wild-type and knockout mice contained the following N-acylethanolamines: AEA (8% of total), 2-arachidonoylglycerol (5%), N-oleoylethanolamine (20%), N-palmitoylethanolamine (53%) and N-stearoylethanolamine (14%) [21].
• Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2-arachidonoylglycerol (2-AG), but not anandamide (up to 1 micro M), 15 min before and throughout the ischaemic period, improved myocardial recovery and decreased the levels of coronary CK and LDH [22].
• Administration of synthetic 2-arachidonoylglycerol (2-AG) but not of anandamide, which are two putative endocannabinoids, causes vomiting via its downstream metabolites such as arachidonic acid (AA) and PGs in the least shrew (Cryptotis parva) [23].
• Human vascular endothelial cells were found to generate and release 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, upon stimulation with thrombin or A23187 [24].

Gene context of C13856

• 2-Arachidonoylglycerol (2-AG) was the second endogenous cannabinoid receptor ligand to be discovered [25].
• 2-Arachidonoylglycerol stimulates activator protein-1-dependent transcriptional activity and enhances epidermal growth factor-induced cell transformation in JB6 P+ cells [26].
• 2-Arachidonoylglycerol (2-AG), an endogenous cannabionoid receptor (CB1 and CB2) ligand, enhanced the adhesion of HL-60 cells differentiated into macrophage-like cells to fibronectin and the vascular cell adhesion molecule-1 [27].
• The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) are under the negative control of leptin in the rodent hypothalamus [28].
• Furthermore, our biochemical analysis demonstrates that combined weak mGluR1 activation and mild depolarization in PCs effectively produces 2-arachidonoylglycerol (2-AG), a candidate of endocannabinoid, whereas either stimulus alone did not produce detectable 2-AG [29].

Analytical, diagnostic and therapeutic context of C13856

• When further optimizing G-protein activation assay for the labile endocannabinoid 2-arachidonoylglycerol (2-AG), we show, by using HPLC, that pretreatment of cerebellar membranes with methyl arachidonoyl fluorophosphonate (MAFP) fully prevented enzymatic degradation of 2-AG and concomitantly enhanced the potency of 2-AG [30].
• Interestingly, epicutaneous treatment with an ether-linked analogue of endogenous cannabinoids, 2-arachidonoylglycerol, caused an ear swelling that could be detected at 1 h, 24 h, and 8 days after treatment of both BALB/c and C57BL/6 mice [31].
• We conclude that the actions following exogenous administration of 2-arachidonoylglycerol were eliminated by direct hemoperfusion through immobilized polymyxin B fibers [14].
• This review will provide a comprehensive evaluation of the roles of the endocannabinoids 2-arachidonoylglycerol and anandamide in stress-induced analgesia [32].
• Chemical ionization gas chromatography and mass spectrometry were also used to determine changes in serum levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), and oleylethanolamide (OEA) [33].

References