Hillard C J, Wilkison D M, Edgemond W S, Campbell W B
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
Biochim Biophys Acta. 1995 Aug 3;1257(3):249-56. doi: 10.1016/0005-2760(95)00087-s.
Arachidonoylethanolamide or 'anandamide' is a naturally occurring derivative of arachidonic acid that has been shown to activate cannabinoid receptors in the brain. Its metabolic inactivation by brain tissue has been investigated. Anandamide is hydrolyzed by the membrane fraction of rat brain homogenate to arachidonic acid and ethanolamine. The hydrolysis is temperature and pH- dependent (pH maximum at 8.5) and abolished by boiling. Anandamide hydrolysis is protein dependent in the range of 25-100 micrograms protein/ml; does not require calcium and is inhibited by phenylmethylsulfonylfluoride, diisopropylfluorophosphate, thimerosal and arachidonic acid. Hydrolysis of 10 microM anandamide by brain membranes follows first order kinetics; at 30 degrees C, the rate constant for anandamide catabolism is 0.34 min-1 mg protein-1. The Km for anandamide hydrolysis is 3.4 microM, and the Vmax is 2.2 nmol/min per mg protein. Hydrolysis occurs in all subcellular fractions except cytosol with the highest specific activity in myelin and microsomes. The distribution of anandamide hydrolytic activity correlates with the distribution of cannabinoid receptor-binding sites; the hippocampus, cerebellum and cerebral cortex exhibit the highest metabolic activity, while activity is lowest in the striatum, brain stem and white matter.
花生四烯酸乙醇酰胺或“阿南德酰胺”是一种天然存在的花生四烯酸衍生物，已被证明可激活大脑中的大麻素受体。其在脑组织中的代谢失活情况已得到研究。阿南德酰胺被大鼠脑匀浆的膜部分水解为花生四烯酸和乙醇胺。该水解反应依赖于温度和pH值（pH最大值为8.5），煮沸可使其失活。阿南德酰胺水解反应在25 - 100微克蛋白质/毫升范围内依赖于蛋白质；不需要钙，且受苯甲基磺酰氟、二异丙基氟磷酸、硫柳汞和花生四烯酸抑制。脑膜对10微摩尔阿南德酰胺的水解遵循一级动力学；在30℃时，阿南德酰胺分解代谢的速率常数为0.34分钟-1毫克蛋白质-1。阿南德酰胺水解的Km值为3.4微摩尔，Vmax为每毫克蛋白质2.2纳摩尔/分钟。除胞质溶胶外，所有亚细胞组分中均发生水解反应，髓磷脂和微粒体中的比活性最高。阿南德酰胺水解活性的分布与大麻素受体结合位点的分布相关；海马体、小脑和大脑皮层的代谢活性最高，而纹状体、脑干和白质中的活性最低。
