Daujat M, Peryt B, Lesca P, Fourtanier G, Domergue J, Maurel P
INSERM U-128, CNRS, BP 5051, Montpellier, France.
Biochem Biophys Res Commun. 1992 Oct 30;188(2):820-5. doi: 10.1016/0006-291x(92)91130-i.
Omeprazole is a benzimidazole derivative which induces both P450 1A1 and 1A2 in human liver in vitro and in vivo. Northern blot analysis of polyA RNA prepared from primary cultures of human hepatocytes indicates that both 1A1 and 1A2 messages are induced by beta-naphthoflavone and omeprazole. Co-treatment of cells with these inducers and with actinomycin D or cycloheximide results in no accumulation of both mRNA or superinduction of 1A1 mRNA, respectively. 9S enriched fraction of cytosol was prepared either from human hepatocytes in culture or from human liver tissue and analyzed by sucrose density gradient sedimentation for its capacity to bind 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole or omeprazole sulfone (a metabolite of omeprazole in man). Whereas 2 microM TCDD displaced almost totally [3H]TCDD from the Ah receptor, both omeprazole and omeprazole sulfone did not, even at 5000-fold molar excess. In addition, when [14C] omeprazole was incubated with 9S enriched fraction of human liver or hepatocyte cytosol, no interaction could be detected in sucrose density gradient. These experiments suggest that omeprazole is not a ligand for the human liver Ah receptor.
奥美拉唑是一种苯并咪唑衍生物，在体外和体内均可诱导人肝脏中的P450 1A1和1A2。对从人肝细胞原代培养物中制备的多聚腺苷酸RNA进行的Northern印迹分析表明，β-萘黄酮和奥美拉唑均可诱导1A1和1A2信息。用这些诱导剂与放线菌素D或环己酰亚胺共同处理细胞，分别不会导致两种mRNA的积累或1A1 mRNA的超诱导。从培养的人肝细胞或人肝脏组织中制备9S富集的细胞溶质部分，并通过蔗糖密度梯度沉降分析其结合2,3,7,8-四氯二苯并-对-二恶英（TCDD）、奥美拉唑或奥美拉唑砜（人体内奥美拉唑的一种代谢产物）的能力。虽然2μM TCDD几乎完全从Ah受体上置换了[3H]TCDD，但即使在摩尔过量5000倍的情况下，奥美拉唑和奥美拉唑砜也不能。此外，当[14C]奥美拉唑与人肝脏或肝细胞溶质的9S富集部分一起孵育时，在蔗糖密度梯度中未检测到相互作用。这些实验表明奥美拉唑不是人肝脏Ah受体的配体。
