Generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain

The levels of 2-arachidonoylglycerol, an endogenous cannabinoid receptor li gand, and other molecular species of monoacylglycerols in rat brain were ex amined. In this study, we sacrificed the animals in liquid nitrogen to mini mize postmortem changes. We found that rat brain contains 0.23 nmol/g tissu e of 2-arachidonoylglycerol, which accounts for 10.5% of the total monoacyl glycerol present in this tissue. We next investigated the:level of 2-arachi donoylglycerol after in vivo stimulation with picrotoxinin. We found that t he level of 2-arachidonoylglycerol was elevated markedly in picrotoxinin-ad ministered rat brain (4- to 6-fold over the control level). Changes in the levels of other molecular species were relatively small or negligible. Seve ral cannabimimetic molecules as well as Delta(9)-tetrahydrocannabinol are k nown to depress neurotransmission and to exert anticonvulsant activities; e ndogenous 2-arachidonoylglycerol produced during neural excitation may play a regulatory role in calming the enhanced synaptic transmission. (C) 2000 Academic Press.