Neutral protease activity and erythropoietin production in the rat after cobalt administration

The generation of erythropoietin purportedly involves the interaction of an enzyme, of renal origin, and a circulating plasma protein substrate. Cobalt, which has the capacity to stimulate erythropoietin formation, was evaluated for its effects on renal and plasma protease activity; in addition, the nature of the erythrogenic mechanism was investigated. Rats receiving one s.c. injection of cobalt demonstrated significant increases in activity of renal cathepsins A and B. The activity of a plasma protease was also elevated in rats after cobalt treatment. Cathepsins A and B and plasma protease were sensitive to the same enzymatic inhibitory agents, and all three enzymes demonstrated activity patterns similar to that of the renal erythropoietic factor [enzyme(s) presumed responsible for generating erythropoietin] in rats treated with cobalt. These data may help to elucidate the mechanism of erythropoiesis.