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

Abstract

[ 185W] tetrathiotungstate was employed to study the metabolism of thiocompounds in rats after i.v. injection. At tracer levels (12.5 μg 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.