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硫代钨酸盐-铜的相互作用。I. 大鼠体内[185W]四硫代钨酸盐的代谢及标记药物剂量与铜的全身相互作用研究。

Thiotungstate-copper interactions. I. Studies on the metabolism of [185W] tetrathiotungstate and the systemic interactions of labeled pharmacological doses with copper in rats.

作者信息

McQuaid A, Lamand M, Mason J

机构信息

Biochemistry Department, Trinity College, Dublin University, Ireland.

出版信息

J Inorg Biochem. 1994 Feb 15;53(3):191-203. doi: 10.1016/0162-0134(94)80004-9.

DOI:10.1016/0162-0134(94)80004-9
PMID:8133255
Abstract

[185W] tetrathiotungstate was employed to study the metabolism of thiocompounds in rats after i.v. injection. At tracer levels (12.5 micrograms W) the most important plasma binding protein eluted in the position of ceruloplasmin but the association did not prevent uptake of thiotungstate by the liver. At higher dose levels (1.5 mg W) there was considerable hydrolysis immediately after injection with rapid excretion of label in urine. The [185W] tetrathiotungstate remaining in plasma was associated with albumin and the amount retained was increased by pretreatment of the rats with copper. The increased binding to albumin did not prevent hepatic uptake and over the short-term pretreatment with copper increased the movement of the isotope into subcellular organelles, probably lysosomes. The excretion in bile was increased and the label was associated with high molecular weight proteins. In liver cytosol the 185W was bound by specific, as yet uncharacterized, proteins. At the higher dose levels there was some movement to higher molecular weight proteins and this was greatly increased by the pretreatment with copper. The studies show that the metabolism of 185W tetrathiotungstate is sufficiently similar to 99Mo or 35S tetrathiomolybdate for work on the systemic interactions of thiocompounds and copper in man and animals.

摘要

[185W]四硫代钨酸盐用于研究大鼠静脉注射后硫化合物的代谢。在示踪剂水平(12.5微克钨)时,最重要的血浆结合蛋白在铜蓝蛋白的位置洗脱,但这种结合并不妨碍肝脏对硫代钨酸盐的摄取。在较高剂量水平(1.5毫克钨)时,注射后立即有大量水解,标记物迅速经尿液排泄。血浆中残留的[185W]四硫代钨酸盐与白蛋白结合,用铜预处理大鼠可增加保留量。与白蛋白结合的增加并不妨碍肝脏摄取,短期内用铜预处理可增加同位素向亚细胞细胞器(可能是溶酶体)的转运。胆汁排泄增加,标记物与高分子量蛋白质相关。在肝细胞溶胶中,185W与特定的、尚未鉴定的蛋白质结合。在较高剂量水平时,会有一些向高分子量蛋白质的转移,用铜预处理可大大增加这种转移。研究表明,185W四硫代钨酸盐的代谢与99Mo或35S四硫代钼酸盐足够相似,可用于研究人和动物体内硫化合物与铜的系统相互作用。

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