Transport of silver in virgin and lactating rats and relation to copper

Virgin and lactating Sprague Dawley rats were used to determine whether the pathways of silver transport to tissues and milk resemble those for copper. Rats were injected i.p. with small amounts of 110AgNO3. Blood and tissues were examined at various times thereafter for total radioactivity and for incorporation into copper binding proteins in plasma and milk. As with 67Cu, much of the 110Ag was rapidly incorporated into the liver. Skeletal muscle, spleen, mammary gland, ovaries, uterus and adrenals also were significant initial accumulation sites, with or without lactation. Lactation enhanced uptake by the mammary gland, and radioactivity rapidly entered the milk and milk ceruloplasmin. In the plasma, most of the 110Ag bound to a single component of apparent molecular weight 800 k throughout the 52 h period examined. A small proportion was also incorporated into plasma ceruloplasmin, as determined by immunoprecipitation and native gel electrophoresis. There was little or no association of 110Ag with albumin or transcuprein. The binding of 110Ag to the 800 kDa protein was tight. Off rates during pH 7 dialysis were <2.5%/day even in the presence of 100 M histidine or Cu(II), but were accelarated by mercaptoethanol. Subunits of 145 and 45 kDa in virtually pure peak fractions were those of α1-macroglobulin. We conclude that silver resembles copper in aspects of its tissue distribution, response to lactation, and incorporation into ceruloplasmin. However its main plasma carrier appears to be α1-macroglobulin, a different macroglobulin than that involved in copper transport.