Erythropoietin induces rapid increases in intracellular free calcium in human bone marrow cells

Elevation of intracellular free calcium (Ca⁺⁺) is an early activation event that occurs as a result of ligand binding in several human cell systems. In this report, erythropoietin, the major hormone governing erythroid differentiation, was found to elicit an increase in Ca⁺⁺ in human bone marrow mononuclear cells. Two chelators of intracellular calcium, quin 2 and the more specific and sensitive analogue, fura-2, were used to characterize the response evoked by both recombinant and native hormone. Erythropoietin caused a rapid, dose-dependent rise (within seconds) in Ca⁺⁺ in bone marrow mononuclear cells, which could be prevented by preincubation of hormone with a rabbit erythropoietin antiserum. The erythropoietin response did not occur in purified populations of T- or B-lymphocytes. These studies suggested that increased Ca⁺⁺ on erythropoietin binding may be an early transmembrane signal in hormone action.