Biosynthesis and metabolism of cannabimimetic anandamide

大麻素是大麻的生物活性成分。外源性大麻素的受体较早被分离，并克隆了它们的cdna。作为大麻素受体的内源性配体，花生四烯醇酰胺被分离出来，称为anandamide。为了更好地了解大麻酰胺的生理功能，需要对大麻酰胺的生物合成和代谢进行研究。日本、意大利和美国的研究小组进行了一项国际合作项目，获得了以下实验结果。1)早前，Ueda等人利用部分纯化的猪脑酶证实了anandamide可能的可逆水解和合成，现在通过过度表达大鼠肝脏类似酶的cDNA制备的重组酶证实了这一点。2)日本、美国和意大利研究组合作筛选了阿南达胺酰胺水解酶选择性抑制剂，发现花生四烯酮（arachidonoyldiazom甲酮）的抑制作用最强，3 ~ 6个muM的IC_<50>值。2-花生四烯醇甘油最近被证明是大麻素受体的另一种配体。日本和意大利的研究小组证实，花生四烯醇和2-花生四烯醇甘油被同一种酶水解。Piomelli等人认为这些配体介导了长期增强。

Cannabinoids are bioactive components of marijuana. Receptors for the exogenous cannabinoids were earlier isolated, and their cDNAs were cloned. As an endogenous ligand for the cannabinoid receptors, arachidonoylethanolamide was isolated and referred to as anandamide. A better understanding of the physiological function of anandamide requires the studies on the biosynthesis and metabolism of anandamide. An international collaboration project was carried out by Japanese, Italian and American reearch groups, and the following experimental results were obtained.1) A possible reversible hydrolysis and synthesis of anandamide was earlier demonstrated by Ueda et al.using a partially purified enzyme of porcine brain, and was now confirmed by the use of a recombinant enzyme prepared by overexpression of cDNA of a similar enzyme of rat liver.2) Selective inhibitors of anandamide amidohydrolase were screened in collaboration of Japanese, American and Italian groups, and arachidonoyldiazomethylketone was found to be most inhibitory with IC_<50> values of 3-6 muM.3) 2-Arachidonoylglycerol was recently shown to be another ligand to cannabinoid receptors. Japanese and Italian groups demonstrated that both anandamide and 2-arachidonoylglycerol were hydrolyzed by the same enzyme.Piomelli et al.suggested taht these ligands mediated lon-term potentiation.