COTININE AND NICOTINE INHIBIT HUMAN-FETAL ADRENAL 11-BETA-HYDROXYLASE
COTININE AND NICOTINE INHIBIT HUMAN-FETAL ADRENAL 11-BETA-HYDROXYLASE
复制标题
DOI：
10.1210/jcem-69-6-1221
复制
发表时间：
1989-12-01
影响因子：
5.8
通讯作者：
OSATHANONDH, R
中科院分区：
文献类型：
--
作者：
BARBIERI, RL;FRIEDMAN, AJ;OSATHANONDH, R
尼古丁和可替宁对胎儿肾上腺11 β的作用和21-羟化酶进行了检查，使用酶和光谱技术。此外，尼古丁或可替宁肾上腺线粒体制剂产生了II型细胞色素P-450结合谱。尼古丁和可替宁与线粒体细胞色素P-450结合的表观光谱解离常数（Ks）分别为20和19 μ M。向肾上腺微粒体制剂中加入尼古丁产生II型细胞色素P-450结合谱，表观Ks为70 μ M。肾上腺线粒体11 β-通过测量脱氧皮质酮向皮质酮的转化来测定羟化酶。尼古丁和可替宁竞争性抑制11 β-羟化酶，表观米氏抑制常数（Ki）分别为9.9和9.0 μ M。尼古丁竞争性抑制微粒体21-羟化酶，表观Ki为110 μ M。浓度高达1 mM的可替宁不抑制21-羟化酶。这些结果表明尼古丁和可替宁抑制11 β-通过与该酶系统的细胞色素P-450组分的血红素铁结合，可以使羟化酶水解。抑制11 β-羟化酶可能有助于在吸烟者中观察到的类固醇生成模式的改变。
The effects of nicotine and cotinine of fetal adrenal 11.beta.- and 21-hydroxylase were examined using enzymatic and spectral techniques. The addition of nicotine or cotinine to preparations of adrenal mitochondria yielded a type II cytochrome P-450 binding spectrum. The apparent spectral dissociation constants (Ks) for nicotine and cotinine binding to mitochondrial cytochrome P-450 were 20 and 19 .mu.M, respectively. The addition of nicotine to preparations of adrenal microsomes yielded a type II cytochrome P-450 binding spectrum, with an apparent Ks of 70 .mu.M. Adrenal mitochondrial 11.beta.-hydroxylase was assayed by measuring the conversion of deoxycorticosterone to corticosterone. Nicotine and cotinine competitively inhibited 11.beta.-hydroxylase, with apparent Michaelis-Menten inhibition constants (Ki) of 9.9 and 9.0 .mu.M, respectively. Nicotine competitively inhibited microsomal 21-hydroxylase, with an apparent Ki of 110 .mu.M. Cotinine, in concentrations as high as 1 mM, did not inhibit 21-hydroxylase. These results suggest that nicotine and cotinine inhibit 11.beta.-hydroxylase by binding to the heme iron of the cytochrome P-450 component of this enzyme system. Inhibition of 11.beta.-hydroxylase could contribute to the altered pattern of steroidogenesis observed in smokers.