title: Microglia produce and hydrolyze palmitoylethanolamide.
abstract: Microglial cell activation and migration play an important role in neuroinflammation propagation. While it is known that the lipid transmitter palmitoylethanolamide (PEA) regulates microglial migration by interacting with a cannabinoid-like receptor, the production and inactivation of this lipid by microglia has never been addressed directly. Here we show that the mouse microglial cell line BV-2 produces and hydrolyzes PEA. The carbamate compound URB602 inhibits PEA hydrolysis in BV-2 cell homogenates and increases PEA levels in intact cells, whereas the FAAH inhibitor URB597 and serine-hydrolase inhibitor MAFP do not affect PEA levels in intact cells. This unique pharmacological profile of inhibitors on PEA hydrolysis suggests the involvement of a previously undescribed enzyme that degrades PEA. This enzyme expressed by microglia constitutes a promising target for controlling the propagation of neuroinflammation.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Nephi
authors.initials: N
authors.lastname: Stella
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006868:Hydrolysis / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010169:Palmitic Acids / Q000378:metabolism*; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D001713:Biphenyl Compounds; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D010169:Palmitic Acids; D000099252:Fatty Acid Amide Hydrolases; C501835:URB602; C005958:palmidrol