USE OF ISOLATED KIDNEY-CELLS FOR STUDY OF DRUG-METABOLISM
USE OF ISOLATED KIDNEY-CELLS FOR STUDY OF DRUG-METABOLISM
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DOI：
10.1016/0006-2952(79)90378-2
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发表时间：
1979-01-01
影响因子：
5.8
通讯作者：
ORRENIUS, S
中科院分区：
文献类型：
--
作者：
JONES, DP;SUNDBY, GB;ORRENIUS, S
采用胶原酶再循环灌注系统从大鼠肾脏制备离体肾细胞。制备快速，并提供了高产量的完整的代谢活性肾细胞主要是管状起源。呼吸速率为2.7 μ mol O2/h/106个细胞，并且不受ADP刺激。GSH [还原型谷胱甘肽]含量为28.9 nmol/106个细胞，在孵育2小时期间未下降。细胞色素P450含量为0.064 nmol/106个细胞。使用扑热息痛[一种常用的镇痛剂]作为底物，对细胞的药物代谢活性进行表征。葡萄糖醛酸苷和硫酸盐衍生物的形成速率在2小时内呈线性，但比先前报告的大鼠肝细胞慢。未检测到谷胱甘肽结合物。观察到半胱氨酸和N-乙酰半胱氨酸衍生物的形成。总巯基结合物的形成率约为50%的肝细胞时，细胞色素P450的基础上表示的报告。该细胞制剂作为研究肾脏药物代谢的模型系统的可靠性和实用性得到了证实。
Isolated kidney cells were prepared from rat kidneys using a recirculating perfusion system with collagenase. The preparation was rapid and provided a high yield of intact metabolically active kidney cells predominantly of tubular origin. The respiration rate was 2.7 .mu.mol O2/h per 106 cells and was not stimulated by ADP. GSH [reduced glutathione] content was 28.9 nmol/106 cells and did not decline during 2 h of incubation. Cytochrome P450 content was 0.064 nmol/106 cells. The cells were characterized for their drug metabolizing activity using paracetamol [a commonly used analgesic] as substrate. The rate of formation of the glucuronide and sulfate derivatives was linear for 2 h but slower than previously reported for rat liver cells. No glutathione conjugate was detected. Formation of both cysteine and N-acetylcysteine derivatives was observed. The rate of formation of total sulfhydryl conjugates was about 50% of that reported for liver cells when expressed on a cytochrome P450 basis. The reliability and utility of this cell preparation as a model system for the study of drug metabolism by the kidney was shown.