Biochemistry and pharmacology of arachidonylethanolamide, a putative endogenous cannabinoid. J Lipid Res 1997 Dec;38(12):2383-98
Date
02/11/1998Pubmed ID
9458263Scopus ID
2-s2.0-0031443586 (requires institutional sign-in at Scopus site) 96 CitationsAbstract
This review presents and explores the hypothesis that N-arachidonylethanolamine (AEA, also called anandamide) is synthesized in the brain and functions as an endogenous ligand of the cannabinoid receptor. Support for this hypothesis comes from in vitro experiments demonstrating that AEA binds and activates signaling through the cannabinoid receptor. In addition, in vivo AEA produces effects very similar to those of the classical agonists of the cannabinoid receptor. Evidence for the cellular synthesis and release of AEA is not as clear. Data are presented that suggest that AEA is synthesized via a two enzyme process. First, a novel phospholipid (N-arachidonylphosphatidylethanolamine) is formed by a calcium-dependent transacylase. This lipid is a substrate for a phosphodiesterase of the phospholipase D type which releases AEA. Although there is some evidence to support this hypothesis, it is clear that AEA is a very minor product of this enzymatic cascade. Several important questions remain to be answered, including whether the concentrations of AEA synthesized by cells are sufficient to support a signaling role in the brain.
Author List
Hillard CJ, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinCecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcyltransferasesAnimals
Arachidonic Acids
Biological Transport
Brain
Cannabinoids
Endocannabinoids
Hydrolysis
Hydroxylation
Phosphatidylethanolamines
Polyunsaturated Alkamides
Protein Binding
Receptors, Cannabinoid
Receptors, Drug
