Abstract
2‐Arachidonoylglycerol (2‐AG) is a unique molecular species of monoacylglycerol identified as an endogenous cannabinoid receptor ligand by us and Mechoulam and co‐workers (1). We found that 2‐AG possesses binding activity toward the cannabinoid receptor in rat brain. We also found that 2‐AG induces transient elevation of the intracellular Ca2+ concentration in NG108‐15 cells. The response induced by 2‐AG was blocked by pretreatment of cells with a cannabinoid CB1 receptor‐specific antagonist SR141716A, indicating that CB1 receptor is involved in the response. Based on the results of structure–activity relationship experiments, we concluded that the cannabinoid CB1 receptor in the nervous system is originally and primary a 2‐AG receptor. 2‐AG was produced and released from nervous tissues following various types of stimulation through enhanced breakdown of arachidonic acid‐containing phospholipids such as inositol phospholipids. Physiological and pathophysiological roles of 2‐AG in the nervous system will be discussed.
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