N-ARACHIDONOYLETHANOLAMINE (ANANDAMIDE), AN ENDOGENOUS CANNABINOID RECEPTOR-LIGAND, AND RELATED LIPID MOLECULES IN THE NERVOUS TISSUES

The effects of N-arachidonoylethanolamine (anandamide) and related com pounds on the binding of [H-3]CP55940 to rat brain synaptosomes were e xamined. Anandamide was shown to inhibit competitively the specific bi nding of [H-3]CP55940 to synaptosomal membranes. The K-i value was 89 nM. In contrast, N-acylethanolamine containing saturated or monoenoic fatty acids did not exhibit high binding affinity. Several structural analogues of anandamide showed some binding activity. Among them, 2-ar achidonoylglycerol is noteworthy because of its occurrence in mammalia n tissues. A biosynthetic study indicated that anandamide can be synth esized via two separate synthetic pathways. The first is synthesis fro m free arachidonic acid and ethanolamine, and the second is the format ion of N-arachidonoyl phosphatidylethanolamine (PE) from diarachidonoy l phospholipids and PE and the subsequent enzymatic release of N-arach idonoylethanolamine. The latter pathway appears to explain very well t he fatty acid composition of N-acylethanolamines present in mammalian tissues.