Structures and Function of Novel Esterase and Amidohydrolase

1)ES46.5K是一种新型的酯酶，它对四氢大麻酚(THC)代谢产物的乙酰基衍生物具有立体选择性和区域选择性的水解性。2)ES46.5K能水解乙酰氨基荧酮、邻苯二甲酸酯、可卡因和海洛因，提示该酶对异源酯类的代谢酶有一定的作用。3)以人AAF-DAC的cDNA为探针，正在进行ES46.5K的克隆。4)天然大麻素(THC、大麻二酚、大麻酚)及其部分代谢产物对小鼠脑微粒体中的氨基水解酶有抑制作用。5)从小鼠肝微粒体中分离纯化了氨基水解酶。6)制备了抗体。7)从小鼠肝脏中筛选出抗体反应性克隆。8)在THC、THC代谢物和Anandamide的同源和低温作用下形成了耐受性和交叉耐受性。此外，还证实了大麻素类化合物与双胺类药物之间的药理作用。

1) ES46.5K, a novel esterase, hydrolyzed stereospecifically and regioselectively the acetyl derivatives of tetrahydrocannabinol (THC) metabolites.2) ES46.5K could hydrolze acetylaminofluorene, phthalate esters, cocaine and heroin, suggesting that the enzyme has some role for metabolizing enzyme of xenobiotic esters.3) cDNA cloning of ES46.5K is in progress using cDNA of human AAF-DAC as a probe.4) Natural cannabinoids (THC, cannabidiol, cannabinol) and some of THC metabolites inhibited anandamide amidohydrolase in mouse brain microsomes.5) Anandamide amidohydrolase was purified from mouse hepatic microsomes and characterized its properties. It is demonstrated that the enzyme has an important role for regulation of biological effects of anandamide.6) The antibody against anandamide amidohydrolase was prepared.7) The Antibody-reactive clones were obtained by screening of cDNA library from mouse liver.8) Tolerance and cross-tolerance developed in the cataleptogenic and hypothermic effect of THC, THC metabolites and anandamide. Pharmacologic interaction between the cannabinoids and anandamide was also demonstrated.