Bonkovsky H L, Hauri H P, Marti U, Gasser R, Meyer U A
Gastroenterology. 1985 Feb;88(2):458-67. doi: 10.1016/0016-5085(85)90507-4.
We have studied total cytochrome P450 and the major form of cytochrome P450 increased by phenobarbital in small intestinal epithelial cells and livers of male Sprague-Dawley rats. Using an improved method for preparing microsomes from intestinal epithelial cells, we find that concentrations of total cytochrome P450 in intestinal cell microsomes are 10% of those in liver microsomes, and that this percentage is unchanged after phenobarbital treatment. In untreated rats, less than 5% of total cytochrome P450 of liver or intestinal epithelium is the form induced by phenobarbital, as measured by rocket immunoelectrophoresis. In phenobarbital-treated rats, the major phenobarbital-induced form accounts for approximately 50% of the total in both organs. In the small intestine of phenobarbital-treated rats, the concentrations of total cytochrome P450 and of the major phenobarbital-induced form increase concurrently as epithelial cells mature from crypt to upper villus. Concentrations of total cytochrome P450 and of the major phenobarbital-induced form in the proximal two-thirds of the rat small intestine are twofold higher than in the distal third. Immunoblotting performed with a monoclonal antibody to the major phenobarbital-induced form of cytochrome P450 from rat liver revealed a subtle difference between this form in liver and intestine.
我们研究了雄性斯普拉格-道利大鼠小肠上皮细胞和肝脏中的总细胞色素P450以及由苯巴比妥诱导增加的主要细胞色素P450形式。使用一种改进的从肠道上皮细胞制备微粒体的方法,我们发现肠道细胞微粒体中总细胞色素P450的浓度是肝脏微粒体中浓度的10%,并且在苯巴比妥处理后这个百分比没有变化。在用火箭免疫电泳测量时,在未处理的大鼠中,肝脏或肠道上皮中总细胞色素P450的不到5%是由苯巴比妥诱导的形式。在经苯巴比妥处理的大鼠中,主要的苯巴比妥诱导形式在两个器官中均占总量的约50%。在经苯巴比妥处理的大鼠小肠中,随着上皮细胞从隐窝到绒毛上部成熟,总细胞色素P450和主要的苯巴比妥诱导形式的浓度同时增加。大鼠小肠近端三分之二处的总细胞色素P450和主要的苯巴比妥诱导形式的浓度比远端三分之一处高两倍。用针对大鼠肝脏中主要的苯巴比妥诱导形式的细胞色素P450的单克隆抗体进行免疫印迹分析,揭示了这种形式在肝脏和肠道中的细微差异。