POTENTIAL BIOSYNTHETIC CONNECTIONS BETWEEN THE 2 CANNABIMIMETIC EICOSANOIDS, ANANDAMIDE AND 2-ARACHIDONOYL-GLYCEROL, IN MOUSE NEUROBLASTOMA-CELLS

Anandamide (arachidonoyl-ethanolamide, AnNH) and 2-arachidonoyl-glycer ol (2-AG) have been suggested to act as endogenous agonists at the bra in cannabinoid receptor, and their biosynthetic and degradative mechan isms in nervous tissues and cells have also been partially elucidated. Here we present evidence for the presence, in mouse N(18)TG(2) neurob lastoma cells, of enzymatic activities potentially responsible for the biosynthesis of AnNH and 2-AG from a common phospholipid precursor. C ell homogenates were shown to catalyze: (a) the transfer of an arachid onoyl moiety from the sn-1 position of sn-1,2-di-arachidonoyl-phosphat idylcholine (AAPC) to phosphatidyl-ethanolamine (PE) to form N-arachid onoyl-PE (N-ArPE) and sn-1-lyso-2-arachidonoyl-PC (lyso-APC), (b) the hydrolysis of N-ArPE to AnNH, (c) the hydrolysis of lyso-APC to 2-AG, (d) the hydrolysis of AAPC to sn-1,2-di-arachidonoyl-glycerol (AAG), a nd (e) the hydrolysis of AAG to 2-AG. From these findings it is possib le to suggest that AAPC may serve as precursor for both AnNH and 2-AG biosynthesis through three different pathways. (C) 1996 Academic Press , Inc.