Evelo C T, Versteegh J F, Blaauboer B J
Xenobiotica. 1984 May;14(5):409-16. doi: 10.3109/00498258409151429.
The rates of secretion of 4-aminophenol and its sulphate and glucuronide conjugate were determined in cultures of rat hepatocytes with aniline and 4-aminophenol as substrates. When 4-aminophenol (300 microM) was used as substrate, 4-aminophenol disappeared from the medium within 30 min. Secretion of conjugates continued for more than 60 min, when 70% of the 4-aminophenol had been secreted as conjugates. At a low concn. of 4-aminophenol, the sulphate ester was the main metabolite, while secretion of the glucuronide showed a more than proportional rise ('lag phase') with increasing substrate concn. At higher concn. (greater than 300 microM) about equal amounts of both conjugates were formed. Without inorganic sulphate, sulphation of 4-aminophenol was greatly diminished and the lag phase in glucuronide secretion was not found. With 1 mM aniline as substrate up to 300 microM of conjugated 4-aminophenol was secreted with a linear time-dependence for at least two hours. With aniline as substrate the sulphate ester was the most important conjugate and lag phases in the secretion of both conjugates were minimal. Phenobarbitone pretreatment in vivo stimulated the secretion of conjugated products after incubation with aniline. No dramatic changes in the profile of the lag phases were seen. The differences in the conjugation profiles of both substrates can be explained by taking into consideration the differences in the expected intracellular concentrations.
以苯胺和4-氨基苯酚为底物，在大鼠肝细胞培养物中测定了4-氨基苯酚及其硫酸盐和葡萄糖醛酸共轭物的分泌速率。当以4-氨基苯酚（300微摩尔）为底物时，4-氨基苯酚在30分钟内从培养基中消失。共轭物的分泌持续超过60分钟，此时70%的4-氨基苯酚已作为共轭物分泌。在低浓度的4-氨基苯酚下，硫酸酯是主要代谢产物，而随着底物浓度增加，葡萄糖醛酸共轭物的分泌呈超比例上升（“滞后阶段”）。在较高浓度（大于300微摩尔）时，两种共轭物形成的量大致相等。没有无机硫酸盐时，4-氨基苯酚的硫酸化作用大大减弱，且未发现葡萄糖醛酸共轭物分泌的滞后阶段。以1毫摩尔苯胺为底物时，分泌出高达300微摩尔的共轭4-氨基苯酚，且至少两小时内呈线性时间依赖性。以苯胺为底物时，硫酸酯是最重要的共轭物，两种共轭物分泌的滞后阶段最小。体内苯巴比妥预处理在与苯胺孵育后刺激了共轭产物的分泌。未观察到滞后阶段曲线有显著变化。考虑到预期细胞内浓度的差异，可以解释两种底物共轭情况的差异。
