An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase

• DOI: 10.1194/jlr.m012153
• Publication Date: 2010-11-20T03:55:36Z
• Authors: Jonathan Z. Long; Melanie LaCava; Xin Jin; Benjamin F. Cravatt
• Keywords: Anandamide

Fatty acid amide hydrolase (FAAH) regulates amidated lipid transmitters, including the endocannabinoid anandamide and its N-acyl ethanolamine (NAE) congeners transient receptor potential channel agonists taurines (NATs). Using both FAAH inhibitor PF-3845 FAAH(-/-) mice, we present a global analysis of changes in NAE NAT metabolism caused by disruption central peripheral tissues. Elevations (and other NAEs) were tissue dependent, with most dramatic occurring brain, testis, liver PF-3845-treated or mice. Polyunsaturated NATs accumulated to very high amounts liver, kidney, plasma these animals. The profile brain was markedly different punctuated significant increases long-chain found exclusively FAAH(-/-), but not Suspecting that this difference might reflect slow pathway for biosynthesis, treated mice chronically 6 days observed robust elevations NATs. These studies, taken together, define anatomical temporal features FAAH-mediated metabolism, which are complemented probably influenced kinetically distinguishable biosynthetic pathways produce lipids vivo.