title: Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus.
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.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 8. Szigony u. 43., Budapest, H-1083 Hungary.
authors.forename: Judit K
authors.initials: JK
authors.lastname: Makara
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.forename: Darren
authors.initials: D
authors.lastname: Fegley
authors.forename: Szilárd I
authors.initials: SI
authors.lastname: Szabó
authors.forename: Satish
authors.initials: S
authors.lastname: Kathuria
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.forename: Andrea
authors.initials: A
authors.lastname: Duranti
authors.forename: Andrea
authors.initials: A
authors.lastname: Tontini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005989:Glycerides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000814:Aniline Compounds; D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; C514879:URB 754; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases