Sugiura Takayuki, Waku Keizo
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.
J Biochem. 2002 Jul;132(1):7-12. doi: 10.1093/oxfordjournals.jbchem.a003200.
Delta9-Tetrahydrocannabinol, a major psychoactive component of marijuana, has been shown to interact with specific cannabinoid receptors, thereby eliciting a variety of pharmacological responses in experimental animals and human. In 1990, the gene encoding a cannabinoid receptor (CB1) was cloned. This prompted the search for endogenous ligands. In 1992, N-arachidonoylethanolamine (anandamide) was isolated from pig brain as an endogenous ligand, and in 1995, 2-arachidonoylglycerol was isolated from rat brain and canine gut as another endogenous ligand. Both anandamide and 2-arachidonoylglycerol exhibit various cannabimimetic activities. The results of structure-activity relationship experiments, however, revealed that 2-arachidonoylglycerol, but not anandamide, is the intrinsic natural ligand for the cannabinoid receptor. 2-Arachidonoylglycerol is a degradation product of inositol phospholipids that links the function of cannabinoid receptors with the enhanced inositol phospholipid turnover in stimulated tissues and cells. The possible physiological roles of cannabinoid receptors and 2-arachidonoylglycerol in various mammalian tissues such as those of the nervous system are discussed.
Δ9-四氢大麻酚是大麻的主要精神活性成分，已被证明可与特定的大麻素受体相互作用，从而在实验动物和人类中引发多种药理反应。1990年，编码大麻素受体（CB1）的基因被克隆。这促使人们寻找内源性配体。1992年，N-花生四烯酰乙醇胺（花生四烯酸乙醇胺）作为一种内源性配体从猪脑中分离出来，1995年，2-花生四烯酸甘油酯作为另一种内源性配体从大鼠脑和犬肠道中分离出来。花生四烯酸乙醇胺和2-花生四烯酸甘油酯都表现出各种拟大麻活性。然而，构效关系实验结果表明，2-花生四烯酸甘油酯而非花生四烯酸乙醇胺是大麻素受体的内在天然配体。2-花生四烯酸甘油酯是肌醇磷脂的降解产物，它将大麻素受体的功能与受刺激组织和细胞中增强的肌醇磷脂周转联系起来。本文讨论了大麻素受体和2-花生四烯酸甘油酯在各种哺乳动物组织（如神经系统组织）中的可能生理作用。
