Abstract
The cannabinoid field is currently an active research area. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most characterized endogenous cannabinoids (also known as endocannabinoids). These neuromodulators have been implicated in various physiologically relevant phenomena, including mood (Witkin et al., 2005), the immune response (Ashton, 2007), appetite (Kirkham and Tucci, 2006), reproduction (Wang et al., 2006), spasticity (Pertwee, 2002), and pain (Hohmann and Suplita, 2006). Pharmacological manipulation of AEA and 2-AG signaling should prove to have significant therapeutic applications in disorders linked to endocannabinoid signaling. One way to alter endocannabinoid signaling is to regulate the events responsible for termination of the endocannabinoid signal-cellular uptake and metabolism. However, to pharmacologically exploit AEA and/or 2-AG signaling in this way, we must first gain a better understanding of the proteins and mechanisms governing these processes. This review serves as an introduction to the endocannabinoid system with an emphasis on the proteins and events responsible for the termination of AEA and 2-AG signaling.
Footnotes
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ABBREVIATIONS: AEA, anandamide; 2-AG, 2-arachidonoylglycerol; CB, cannabinoid receptor; PPAR, peroxisome proliferator-activated receptor; FAAH, fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; COX, cyclooxygenase; LOX, lipoxygenase; HETE-EA, hydroperoxyeicosatetraenoylethanolamide; HETE-GE, hydroperoxyeicosatetraenoic acid glycerol ester; TRPV1, transient receptor potential vanilloid receptor 1; LY2318912, 5-((4-azido-3-iodo-benzoylamino)methyl)tetrazole-1-carboxylic acid dimethylamide; AM404, N-(4-hydroxyphenyl)-arachidonoylamide; VDM11, N-(4-hydroxy-2-methylphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide; JZL184, 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)-methyl)piperidine-1-carboxylate.
- Accepted April 23, 2009.
- Received February 3, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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