2-Arachidonoylglycerol: an endogenous cannabinoid receptor agonist

摘要

#DELTA#~9-Tetrahydrocannabinol (#DELTA#~9-THC) is a major psychoactive constituent of marijuana and is known to exert a variety of pharmacological effects on experimental animals and humans. The mechanism of action of #DELTA#~9-THC has long remained uncertain. In 1988, Devane et al. [1] provided evidence for the occurrence of specific binding site(s) for cannabinoids in rat brain synaptosomes using a radiolabeled synthetic cannabinoid, [~3H]CP55940. In 1990, Matsuda et al. [2] cloned a DNA encoding a cannabinoid receptor (CB1 receptor) from a rat brain DNA library. The CB1 receptor is present in various mammalian tissues especially in the nervous tissues and is assumed to be involved in the attenuation of neurotransmission [3]. In 1993, Munro et al. [4] cloned a DNA encoding another type of cannabinoid receptor (CB2 receptor) from an HL-60 DNA library. The CB2 receptor is present mainly in the immune system (e. g. spleen and tonsil) and is supposed to be involved in the regulation of immune responses and/or inflammatory reactions [3], although details have not yet been elucidated. It has generally been assumed that various cannabinoids including #DELTA#~9-THC exert their biological activities mostly through acting on these cannabinoid receptors (CB1 and CB2).