Abstract
2-Arachidonoyl-glycerol (2-AG) and arachidonyl-ethanolamide (AEA) are endocannabinoids that have been implicated in many physiologic disorders, including obesity, metabolic syndromes, hepatic diseases, pain, neurologic disorders, and inflammation. Their immunomodulatory effects are numerous and are not always mediated by cannabinoid receptors, reflecting the presence of an arachidonic acid (AA) molecule in their structure, the latter being the precursor of numerous bioactive lipids that are pro- or anti-inflammatory. 2-AG and AEA can thus serve as a source of AA but can also be metabolized by most eicosanoid biosynthetic enzymes, yielding additional lipids. In this regard, enhancing endocannabinoid levels by using endocannabinoid hydrolysis inhibitors is likely to augment the levels of these lipids that could regulate inflammatory cell functions. This review summarizes the metabolic pathways involved in the biosynthesis and metabolism of AEA and 2-AG, as well as the biologic effects of the 2-AG and AEA lipidomes in the regulation of inflammation.
Keywords:
MAG lipase; anandamide; eicosanoid; leukocyte; leukotriene; prostaglandin.
© Society for Leukocyte Biology.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Arachidonic Acids / immunology
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Arachidonic Acids / metabolism*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / pathology
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Endocannabinoids / immunology
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Endocannabinoids / metabolism*
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Glycerides / immunology
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Glycerides / metabolism*
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Humans
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation / pathology
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Lipid Metabolism / immunology*
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Liver Diseases / immunology
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Liver Diseases / metabolism
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Liver Diseases / pathology
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Lymphocytes / immunology
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Lymphocytes / metabolism*
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Lymphocytes / pathology
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Metabolic Syndrome / immunology
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Metabolic Syndrome / metabolism
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Metabolic Syndrome / pathology
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Neurodegenerative Diseases / immunology
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / pathology
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Obesity / immunology
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Obesity / metabolism
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Obesity / pathology
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Pain / immunology
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Pain / metabolism
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Pain / pathology
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Phosphatidic Acids / immunology
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Phosphatidic Acids / metabolism
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Polyunsaturated Alkamides / immunology
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Polyunsaturated Alkamides / metabolism*
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Receptors, Cannabinoid / immunology
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Receptors, Cannabinoid / metabolism
Substances
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Arachidonic Acids
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Endocannabinoids
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Glycerides
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Phosphatidic Acids
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Polyunsaturated Alkamides
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Receptors, Cannabinoid
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glyceryl 2-arachidonate
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anandamide