Tabarelli-Poplawski S, Uehleke H
Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(1):105-10. doi: 10.1007/BF00508817.
After i.p. injection of 3-14C-antipyrine (10 micronmole = 1.9 mg with 10 micronCi per 10 g of body weight) to mice radioactivity was irreversibly bound to liver proteins. The irreversible binding reached maximal values of 0.15 nmole/mg protein in liver microsomes after 30-60 min. During 60 min incubation with liver microsomes of mice and rabbits (phenobarbital pretreated) and a NAKPH-regenerating system 3-14C-antipyrine was irreversibly bound to microsomal protein at a rate of 1.5 nmole/mg protein (mouse) and 3 nmole/mg protein (rabbit). In identical incubates with rabbit liver microsomes the 4-hydroxylation of antipyrine was 24 nmole/mg protein in 60 min and formaldehyde production from antipyrine 3 nmole/mg protein in 60 min. In incubates with rabbit liver microsomes the binding rate was 80-90% inhibited by 1mM metyrapone, SKF 525-A and trichloropropene epoxide respectively; 4-hydroxylation was 70-80% inhibited by the same substances. In the presence of 1mM GSH, cysteine or ethylene diamine binding was 30-40% inhibited, whereas 4-hydroxylation showed no inhibition.
给小鼠腹腔注射3 - 14C - 安替比林（10微摩尔 = 1.9毫克，每10克体重含10微居里）后，放射性不可逆地与肝脏蛋白质结合。30 - 60分钟后，肝脏微粒体中不可逆结合达到最大值，为0.15纳摩尔/毫克蛋白质。在与小鼠和兔子（经苯巴比妥预处理）的肝脏微粒体以及一个NAKPH再生系统一起孵育60分钟的过程中，3 - 14C - 安替比林以1.5纳摩尔/毫克蛋白质（小鼠）和3纳摩尔/毫克蛋白质（兔子）的速率不可逆地与微粒体蛋白质结合。在与兔肝微粒体的相同孵育中，安替比林的4 - 羟基化在60分钟内为24纳摩尔/毫克蛋白质，安替比林产生甲醛在60分钟内为3纳摩尔/毫克蛋白质。在与兔肝微粒体的孵育中，结合速率分别被1毫摩尔美替拉酮、SKF 525 - A和三氯丙烯环氧化物抑制80 - 90%；4 - 羟基化被相同物质抑制70 - 80%。在1毫摩尔谷胱甘肽、半胱氨酸或乙二胺存在的情况下，结合被抑制30 - 40%，而4 - 羟基化未显示出抑制作用。
