Independent activation of adenylate cyclase by erythropoietin and isoprenaline.

Abstract The possibility that catecholamines modulate the erythropoietin-induced increase in production of cyclic AMP was investigated by examining the effect of erythropoietin and/or l -isoprenaline on the activity of the plasma membrane adenylate cyclase of anaemic rabbit bone marrow erythroblasts. Membranes isolated from cells cultured in the presence of both hormones exhibited both the transient stimulation of basal activity characteristic of erythropoietin action and the loss of the in vitro response to l -isoprenaline, concomitant with the loss of β-adrenergic receptors, characteristic of l -isoprenaline stimulation. The presence of erythropoietin during cell culture with L-isoprenaline had no effect on the desensitization or number of β-adrenergic receptors. The stimulation of adenylate cyclase by erythropoietin was observed also in the presence of the β-antagonist propranolol, when both were added either to whole cells or to isolated membranes. We conclude that these two hormones activate adenylate cyclase independently of each other, via different receptors, with little evidence of cross-modulation.