An Important Role for N-Acylethanolamine Acid Amidase in the Complete Freund's Adjuvant Rat Model of Arthritis

The Journal of Pharmacology and Experimental Therapeutics
F T BonezziDaniele Piomelli

Abstract

The endogenous lipid amides, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), exert marked antinociceptive and anti-inflammatory effects in animal models by engaging nuclear peroxisome proliferator-activated receptor-α. PEA and OEA are produced by macrophages and other host-defense cells and are deactivated by the cysteine amidase, N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and B-lymphocytes. In the present study, we examined whether a) NAAA might be involved in the inflammatory reaction triggered by injection of complete Freund's adjuvant (CFA) into the rat paw and b) administration of 4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]-carbamate (ARN726), a novel systemically active NAAA inhibitor, attenuates such reaction. Injection of CFA into the paw produced local edema and heat hyperalgesia, which were accompanied by decreased PEA and OEA content (assessed by liquid chromatography/mass spectrometry) and increased NAAA levels (assessed by Western blot and ex vivo enzyme activity measurements) in paw tissue. Administration of undec-10-ynyl-N-[(3S)-2-oxoazetidin-3-yl] carbamate (ARN14686), a NAAA-preferring activity-based probe, revealed that NAAA was catalytically active in CFA-treat...Continue Reading

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Citations

Oct 17, 2017·Chemical Communications : Chem Comm·Rita PetraccaDaniele Piomelli
Jun 21, 2017·Pain and Therapy·Jan M Keppel Hesselink
Oct 12, 2018·Proceedings of the National Academy of Sciences of the United States of America·Alexei GorelikBhushan Nagar
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Jul 15, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Andrea GhidiniDaniele Piomelli
Aug 16, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Stefania SgroiAngelo Reggiani

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