Regulation of beta-adrenergic responsiveness during erythroid differentiation of Friend erythroleukemia cells

Mouse erythroblastoma cells were used as a model system to study sensitivity and regulation of the beta-adrenergic system during DMSO-induced differentiation from the proerythroblast to the normoblast stage. Differentiation was characterized by a initial marked increase in hormonal sensitivity lasting 24 to 40 h followed by a gradual loss of beta-adrenergic responsiveness. These changes are mainly due to a rapid but transient increase in receptor density (4 fold) and a marked shift of the membrane concentrations of the transmembrane signalling proteins Gs and Gi. The Gs to Gi ratio changed from 1:7 in native MEL cells to 2:1 in differentiated cells. By contrast, fusion experiments between rat reticulocytes and and MEL cells indicated that cytosolic factors, while not prominently involved in the regulation of the beta-adrenergic system of differentiating MEL cells, may be responsible for the rapid loss of cyclase activity during reticulocyte maturation, the last step in red cell formation.