BIOCHEMISTRY AND PHARMACOLOGY OF ARACHIDONYLETHANOLAMIDE, A PUTATIVE ENDOGENOUS CANNABINOID

This review presents and explores the hypothesis that N-arachidonyleth anolamine (AEA, also called anandamide) is synthesized in the brain an d functions as an endogenous ligand of the cannabinoid receptor. Suppo rt for this hypothesis comes from in vitro experiments demonstrating t hat AEA binds and activates signaling through the cannabinoid receptor . In addition, in vivo AEA produces effects very similar to those of t he classical agonists of the cannabinoid receptor. Evidence for the ce llular synthesis and release of AEA is not as clear. Data are presente d that suggest that AEA is synthesized via a two enzyme process. First , a novel phospholipid (N-arachidonylphosphatidylethanolamine) is form ed by a calcium-dependent transacylase. This lipid is a substrate for a phosphodiesterase of the phospholipase D type which releases AEA. Al though there is some evidence to support this hypothesis, it is clear that AEA is a very minor product of this enzymatic cascade. Several im portant questions remain to be answered, including whether the concent rations of AEA synthesized by cells are sufficient to support a signal ing role in the brain.