Alteration of transit time and direction of flow to probe the heterogeneous distribution of conjugating activities for harmol in the perfused rat liver preparation.
Alteration of transit time and direction of flow to probe the heterogeneous distribution of conjugating activities for harmol in the perfused rat liver preparation.
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改变通过时间和流动方向以探测灌注大鼠肝脏制剂中哈罗酚结合活性的异质分布。
DOI：
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发表时间：
1985
影响因子：
3.5
通讯作者：
K. Pang
中科院分区：
文献类型：
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作者：
J. Dawson;J. G. Weitering;G. Mulder;R. N. Stillwell;K. Pang
以前在一次通过灌注的大鼠肝脏制备中的研究已经表明，底物的正常和逆行递送技术以及肝脏中酶分布的计算机模拟沿着正弦流动路径可用于描绘哈尔酚代谢的硫酸化和葡萄糖醛酸化活性的相对分布（Pang等人，J. Pharmacol. Exp. Ther. 224：647-653，1983）。观察到的骆驼蓬酚的稳态肝脏提取率以及骆驼蓬酚硫酸盐和骆驼蓬酚葡萄糖醛酸苷的稳态形成率与三种酶分布模型一致，这三种模型描述了硫酸化活性的近端定位和葡萄糖醛酸化活性的更远端分布。本研究报告进一步完善了这些活动分布的定义。所用的实验方法包括通过正常流量以8、12和16 ml/min的速度扰动harmol（10 μ M）的递送，以及在单向灌注大鼠肝脏制备中以恒定的肝血流量（8、12或16 ml/min）交替正常和逆行方向流量递送harmol（10 μ M）。将观察到的稳态硫酸化和葡萄糖醛酸化速率与先前证明为适当的模型和其他酶分布模型提供的预测值进行比较。观察到的和预测的数据表明硫酸化活性的门静脉周围分布和骆驼蓬酚代谢的葡萄糖醛酸化活性的均匀分布。
Previous studies in the once-through perfused rat liver preparation have shown that the techniques of normal and retrograde delivery of substrate and computer simulation of enzyme distributions along the sinusoidal flow path in liver were useful in delineating the relative distributions of sulfation and glucuronidation activities for harmol metabolism (Pang et al., J. Pharmacol. Exp. Ther. 224: 647-653, 1983). The observed steady-state hepatic extraction ratios of harmol and the steady-state formation rates of harmol sulfate and harmol glucuronide were consistent with three enzyme-distribution models which described a proximal localization of sulfation activity and a more distal distribution of glucuronidation activities. The present study was a further refinement on the definition of the distribution of these activities. The experimental approach used included the perturbation of delivery of harmol (10 microM) at 8, 12 and 16 ml/min by normal flow, and the alternation of normal and retrograde directional flows for delivery of harmol (10 microM) at constant hepatic blood flows (8, 12 or 16 ml/min) in the single-pass perfused rat liver preparation. The observed steady-state sulfation and glucuronidation rates were compared against predicted values afforded by models previously shown to be adequate and additional enzyme-distributed models. The observed and predicted data point to a periportal distribution of sulfation activity and an even distribution of glucuronidation activity for the metabolism of harmol.