Instituut voor Neuropathische Pijn
English articles Gliopathic pain Palmitoylethanolamide and leucocyte inhibition
| Palmitoylethanolamide and leucocyte inhibition |
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Palmitoylethanolamide (PEA) is a lipid amide that occurs in our bodies as well as in many mammalian tissues, and can when administered as a drug, inhibits inflammatory responses via the recent described nuclear receptor, the peroxisome proliferator-activated receptor-alpha (PPAR-alpha).
PEA is metabolized via hydrolyzattion by the cysteine amidase N-acylethanolamine-hydrolyzing acid amidase (NAAA). This enzyme is highly expressed in macrophages. The selective NAAA inhibitor, N-[(3S)-2-oxo-3-oxetanyl]-3-phenylpropanamide [(S)-OOPP] increases PEA levels in activated leukocytes. This in turn blunts inflammatory responses both in vitro and in vivo. These effects can be mimicked by exogenous PEA, and disappear in absence of PPAR-alpha. The authors stated: The results suggest that PEA activation of PPAR-alpha in leukocytes serves as an early stop signal that contrasts the progress of inflammation. The PEA-hydrolyzing amidase NAAA may provide a previously undescribed target for antiinflammatory medicines.[1] Jan M. Keppel Hesselink, MD, PhD, January 2011 Referenties[1]: Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Rivara S, Mor M, Russo R, Maccarrone M, Antonietti F, Duranti A, Tontini A, Cuzzocrea S, Tarzia G, Piomelli D. | Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. | Proc Natl Acad Sci U S A. | 2009 Dec 8;106(49):20966-71. Epub 2009 Nov 19. |