The postmortal accumulation of brain N-arachidonylethanolamine (anandamide) is dependent upon fatty acid amide hydrolase activity.
N-arachidonylethanolamine (AEA) accumulates during brain injury and postmortem. Because fatty acid amide hydrolase (FAAH) regulates brain AEA content, the purpose of this study was to determine its role in the postmortal accumulation of AEA using FAAH null mice. As expected, AEA content in immediately frozen brain tissue was significantly greater in FAAH-deficient (FAAH-/-) than in wild-type mice. However, AEA content was significantly lower in brains from FAAH-/- mice at 5 and 24 h postmortem. Similarly, wild-type mice treated in vivo with a FAAH inhibitor (URB532) had significantly lower brain AEA content 24 h postmortem compared with controls. These data indicate that FAAH contributes significantly to the postmortal accumulation of AEA. In contrast, the accumulations of two other N-acylethanolamines, N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA), were not reduced at 24 h postmortem in either the FAAH-/- mice or mice treated with URB532. FAAH-/- mice accumulated significantly less ethanolamine at 24 h postmortem compared with wild-type mice, suggesting that FAAH activity plays a role in the accumulation of ethanolamine postmortem. These data demonstrate that FAAH activity differentially affects AEA and OEA/PEA contents postmortem and suggest that AEA formation specifically occurs via an ethanolamine-dependent route postmortem.
Patel
Sachin
S
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
Carrier
Erica J
EJ
Ho
W-S Vanessa
WS
Rademacher
David J
DJ
Cunningham
Sonya
S
Reddy
D Sudarshan
DS
Falck
J R
JR
Cravatt
Benjamin F
BF
Hillard
Cecilia J
CJ
D000577:Amides; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis*; D001921:Brain / Q000378:metabolism*; D063388:Endocannabinoids; D019856:Ethanolamine / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009829:Oleic Acids; D010169:Palmitic Acids / Q000378:metabolism; D018532:Pisum sativum / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D011180:Postmortem Changes; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D019856:Ethanolamine; D004983:Ethanolamines; D009829:Oleic Acids; D010169:Palmitic Acids; D010714:Phosphatidylethanolamines; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C109143:N-arachidonylphosphatidylethanolamine; C033595:N-oleoylethanolamine; C005958:palmidrol; C078814:anandamide