| An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase. | |
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MedLine Citation:
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PMID: 21097653 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fatty acid amide hydrolase (FAAH) regulates amidated lipid transmitters, including the endocannabinoid anandamide and its N-acyl ethanolamine (NAE) congeners and transient receptor potential channel agonists N-acyl taurines (NATs). Using both the FAAH inhibitor PF-3845 and FAAH(-/-) mice, we present a global analysis of changes in NAE and NAT metabolism caused by FAAH disruption in central and peripheral tissues. Elevations in anandamide (and other NAEs) were tissue dependent, with the most dramatic changes occurring in brain, testis, and liver of PF-3845-treated or FAAH(-/-) mice. Polyunsaturated NATs accumulated to very high amounts in the liver, kidney, and plasma of these animals. The NAT profile in brain tissue was markedly different and punctuated by significant increases in long-chain NATs found exclusively in FAAH(-/-), but not in PF-3845-treated animals. Suspecting that this difference might reflect a slow pathway for NAT biosynthesis, we treated mice chronically with PF-3845 for 6 days and observed robust elevations in brain NATs. These studies, taken together, define the anatomical and temporal features of FAAH-mediated NAE and NAT metabolism, which are complemented and probably influenced by kinetically distinguishable biosynthetic pathways that produce these lipids in vivo. |
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Authors:
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Jonathan Z Long; Melanie LaCava; Xin Jin; Benjamin F Cravatt |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-19 |
Journal Detail:
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Title: Journal of lipid research Volume: 52 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-17 Completed Date: 2011-05-05 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 337-44 Citation Subset: IM |
Affiliation:
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The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue, White
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enzymology Amidohydrolases / blood, metabolism* Animals Arachidonic Acids / metabolism Brain / enzymology Enzyme Inhibitors / pharmacology Ethanolamines / metabolism Kidney / enzymology Liver / enzymology Male Mice Piperidines / pharmacology Polyunsaturated Alkamides / metabolism Pyridines / pharmacology Substrate Specificity Taurine / analogs & derivatives, metabolism Testis / enzymology Tissue Distribution |
| Grant Support | |
ID/Acronym/Agency:
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DA-009789/DA/NIDA NIH HHS; DA-017259/DA/NIDA NIH HHS; P01 DA017259-07/DA/NIDA NIH HHS; P01 DA017259-08/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Enzyme Inhibitors; 0/Ethanolamines; 0/PF 3845; 0/Piperidines; 0/Polyunsaturated Alkamides; 0/Pyridines; 107-35-7/Taurine; 94421-68-8/anandamide; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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