CYP3A GENE-EXPRESSION IN HUMAN GUT EPITHELIUM
CYP3A GENE-EXPRESSION IN HUMAN GUT EPITHELIUM
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DOI：
10.1097/00008571-199410000-00003
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发表时间：
1994-10-01
期刊：
影响因子：
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通讯作者：
WATKINS, PB
中科院分区：
文献类型：
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作者：
KOLARS, JC;LOWN, KS;WATKINS, PB
CYP3A4 是肝脏中存在的一种主要的 I 期异生物质代谢酶，也存在于人类小肠上皮中，它似乎可以催化某些药物的显着“首过”代谢。为了确定 CYP3A4 或相关酶 CYP3A3、CYP3A5 和 CYP3A7 是否存在于消化道的其他区域，我们使用 CYP3A 特异性抗体来检查从人体器官捐献者获得的组织学切片和上皮微粒体。在整个消化道的上皮细胞、胃壁细胞、中央周围肝细胞和胰腺导管细胞中检测到 CYP3A 相关蛋白。免疫印迹分析表明，肝脏、空肠、结肠和胰腺中存在的主要 CYP3A 蛋白是 CYP3A4 或 CYP3A3，而胃中存在的主要蛋白是 CYP3A5。使用聚合酶链式反应 (PCR) 可在消化道的所有区域检测到 CYP3A4 和 CYP3A5 mRNA；然而，Northern印迹分析只能检测到CYP3A4。通过 PCR 始终仅在肝脏中检测到 CYP3A7 mRNA，而在任何组织中均未检测到 CYP3A3 mRNA。我们得出的结论是，CYP3A4 和 CYP3A5 存在于整个人类消化道中，这些酶表达的差异可能解释了 CYP3A 底物代谢的器官间差异。
CYP3A4, a major Phase I xenobiotic metabolizing enzyme present in liver, is also present in human small bowel epithelium where it appears to catalyse significant 'first pass' metabolism of some drugs. To determine whether CYP3A4 or the related enzymes CYP3A3, CYP3A5, and CYP3A7 are present in other regions of the digestive tract, we used CYP3A-specific antibodies to examine histological sections and epithelial microsomes obtained from a human organ donor. CYP3A-related proteins were detected in epithelia throughout the digestive tract and in gastric parietal cells, in pericentral hepatocytes, and in ductular cells of the pancreas. Immunoblot analysis suggested that the major CYP3A protein present in liver, jejunum, colon, and pancreas was CYP3A4 or CYP3A3, whereas CYP3A5 was the major protein present in stomach. Both CYP3A4 and CYP3A5 mRNA were detectable in all regions of the digestive tract using the polymerase chain reaction (PCR); however, only CYP3A4 could be detected by Northern blot analysis. CYP3A7 mRNA was consistently detected only in the liver by PCR and CYP3A3 mRNA was not detected in any of the tissues. We conclude that CYP3A4 and CYP3A5 are present throughout the human digestive tract and that differences in the expression of these enzymes may account for inter-organ differences in the metabolism of CYP3A substrates.