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首页> 美国卫生研究院文献>other >Immunochemical detection of cytochrome P450 enzymes in small intestine microsomes of male and female untreated juvenile cynomolgus monkeys
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Immunochemical detection of cytochrome P450 enzymes in small intestine microsomes of male and female untreated juvenile cynomolgus monkeys

机译：免疫化学检测未处理的雄性和食幼食蟹猴小肠微粒体中细胞色素P450酶

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class="enumerated" style="list-style-type:decimal" id="L1">The expression of small intestinal cytochromes P450 (P450s) has not been systematically measured in cynomolgus monkeys, which are widely used in preclinical drug studies to predict pharmacokinetics and toxicity in humans: therefore, P450 content of small intestine was quantified in 35 cynomolgus monkeys by immunoblotting using 11 selective antibodies.CYP2D, CYP2J2, CYP3A4, and CYP3A5 were detected in all 35 animals, while CYP1A and CYP2C9/19 were detected in 31 and 17 animals, respectively. CYP2C9 and CYP2C19 were detected with the same antibody. CYP1D, CYP2A, CYP2B6, CYP2C76, and CYP2E1 were not detected in any of the 35 animals examined.On analysis of pooled microsomes (35 animals), CYP3A (3A4 + 3A5) was most abundant (79% of total immunoquantified CYP1-3 proteins), followed by CYP2J2 (13%), CYP2C9/19 (4%), CYP1A (3%), and CYP2D (0.4%). On analysis of individual microsome samples, each P450 content varied 2- to 6-fold between animals, and no sex differences were observed in any P450 content.These findings should help to increase the understanding of drug metabolism, especially the first-pass effect, in cynomolgus monkey small intestines.
机译：class =“ enumerated” style =“ list-style-type：decimal” id =“ L1”> <！-list-behavior =枚举前缀word = mark-type = decimal max-label-size = 0- -> li>尚未在食蟹猴中系统地测量小肠细胞色素P450（P450s）的表达，食蟹猴广泛用于临床前药物研究，以预测人类的药代动力学和毒性：因此，小肠P450的含量在使用11种选择性抗体通过免疫印迹法对35只食蟹猴进行了检测。 CYP2D，CYP2J2，CYP3A4和CYP3A5在所有35只动物中均被检测到，而CYP1A和CYP2C9 / 19分别在31只和17只动物中被检测到。用同一抗体检测CYP2C9和CYP2C19。在所检查的35只动物中，没有检测到CYP1D，CYP2A，CYP2B6，CYP2C76和CYP2E1。 在分析混合微粒体（35只动物）时，CYP3A（3A4 + 3A5）最丰富（79％总免疫定量CYP1-3蛋白），然后是CYP2J2（13％），CYP2C9 / 19（4％），CYP1A（3％）和CYP2D（0.4％）。在对单个微粒体样品进行分析时，动物之间每个P450含量变化2至6倍，并且在任何P450含量中均未观察到性别差异。 这些发现应有助于增进对药物代谢的了解，尤其是首过效应对食蟹猴小肠的影响。

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