Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated release of inflammatory mediators.
Anandamide and other fatty acid amides are metabolised by the enzyme fatty acid amide hydrolase (FAAH), which thereby regulates their endogenous levels. Here we demonstrate that cultured rat cortical microglia express FAAH at low levels. The potent FAAH inhibitor URB597 reduced the LPS stimulated microglial expression of cyclo-oxygenase 2 and inducible nitric oxide, with concomitant attenuation of the release of PGE2 and NO. Additional of supplemental exogenous anandamide did not increase the magnitude of attenuation of mediator release. The effect of URB597 on LPS stimulated PGE2 release was not blocked by selective CB1 or CB2 receptor antagonists.
Tham
Chui-Se
CS
Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121-1126, United States.
Whitaker
John
J
Luo
Lin
L
Webb
Michael
M
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D014409:Tumor Necrosis Factor-alpha; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C496318:Nos2 protein, rat; C489691:Ptgs2 protein, rat