Endocannabinoid overload |
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Authors: | Lichtman Aron H Blankman Jacqueline L Cravatt Benjamin F |
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Institution: | The Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. alichtma@vcu.edu |
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Abstract: | The signaling capacity of endogenous cannabinoids ("endocannabinoids") is tightly regulated by degradative enzymes. This Perspective highlights a research article in this issue (p. 996) in which the authors show that genetic disruption of monoacylglycerol lipase (MAGL), the principal degradative enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG), causes marked elevations in 2-AG levels that lead to desensitization of brain cannabinoid receptors. These findings highlight the central role that MAGL plays in endocannabinoid metabolism in vivo and reveal that excessive 2-AG signaling can lead to functional antagonism of the brain cannabinoid system. |
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