Long-chain N-acylethanolamines (NAEs) elicit a variety of biological a
nd pharmacological effects. Anandamide (20:4n-6 NAE) and other polyuns
aturated NAEs bind to the cannabinoid receptor and may thus serve as h
ighly specific lipid mediators of cell signalling. NAEs can be: formed
by phospholipase D-catalyzed hydrolysis of N-acylethanolamine phospho
lipids or by direct condensation of ethanolamine and fatty acid. So fa
r, most of the latter biosynthetic activity has been shown to be the r
everse reaction of the NAE amidohydrolase that catalyzes NAE degradati
on. Thus, increasing evidence supports the hypothesis that the iv-acyl
ation-phosphodiesterase pathway yields not only saturated-monounsatura
ted NAEs, but polyunsaturated ones, including anandamide, as well.