Abstract
The functions of 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid found in the brain, remain largely unknown. Here we show that two previously unknown inhibitors of monoacylglycerol lipase, a presynaptic enzyme that hydrolyzes 2-AG, increase 2-AG levels and enhance retrograde signaling from pyramidal neurons to GABAergic terminals in the hippocampus. These results establish a role for 2-AG in synaptic plasticity and point to monoacylglycerol lipase as a possible drug target.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aniline Compounds
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Animals
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Arachidonic Acids / antagonists & inhibitors*
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Arachidonic Acids / metabolism
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Benzoxazines
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Cannabinoid Receptor Modulators
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Dose-Response Relationship, Drug
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Endocannabinoids
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Glycerides / antagonists & inhibitors*
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Glycerides / metabolism
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HeLa Cells
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Hippocampus / cytology*
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Humans
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Hydrolysis / drug effects
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In Vitro Techniques
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Monoacylglycerol Lipases / metabolism
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Neural Inhibition / drug effects
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Patch-Clamp Techniques / methods
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Pyramidal Cells / drug effects*
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Pyramidal Cells / physiology
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Rats
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Signal Transduction / drug effects*
Substances
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Aniline Compounds
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Arachidonic Acids
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Benzoxazines
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Cannabinoid Receptor Modulators
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Endocannabinoids
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Enzyme Inhibitors
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Glycerides
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URB 754
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glyceryl 2-arachidonate
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Monoacylglycerol Lipases