Increased Kidney Cyclic AMP Levels and Erythropoietin Production Following Cobalt Administration 1

Abstract

Summary

The possible role of adenosine-3',5'-monophosphate (cyclic AMP) in mediating the effect of the hormone erythropoietin (ESF) was evaluated. The administration of dibutyryl cyclic AMP (dBcAMP) to exhypoxic polycythemic mice resulted in an increase in radioactive iron (⁵⁹Fe) incorporation in RBC. This ⁵⁹Fe incorporation in RBC was linear with doses of dBcAMP ranging from 300 to 1000 μmoles/kg. This erythropoietic response was partially blocked by the antibody to ESF. Three hours after cobalt administration, kidney cyclic AMP levels were significantly increased over control values. This elevation in cyclic AMP preceded a rise in renal REF activity which reached a maximum 9 hr after cobalt administration. Plasma ESF levels were also elevated reaching a maximum 12 to 15 hr after cobalt treatment. These data suggest that cyclic AMP is involved in the activation and/or production of ESF following cobalt administration.

The authors acknowledge the excellent technical assistance of Mary Catherine Mueller, Phyllis Taylor and Jesse Brookins.