Rauscher murine erythroleukemia cells, grown continuously in vitro, undergo erythroid differentiation in response to the hormone erythropoietin. Therefore, they serve as an important model system with which to examine critical biochemical aspects of this developmental process. Intact, uninduced Rauscher cells possess a functional beta-adrenergic receptor-adenylate cyclase complex. The adrenergic agonists, isoproterenol, epinephrine, and norepinephrine, exhibited activation constants (Kact) of 0.1, 0.5, and 20 mumol/L, respectively. Thus, the beta-receptor-cyclase complex of Rauscher cells is apparently one of the most sensitive of all erythroid cells reported thus far. The epinephrine-stimulated cyclic adenosine monophosphate (cAMP) response was inhibited by propranolol, alprenolol, and hydroxybenzylpindolol, with inhibition constants (KI) of 3.8, 2.2, and 0.1 nmol/L, respectively. Using [125I]-iodohydroxybenzylpindolol as ligand, uninduced Rauscher cells were shown to possess 1,100 receptors/cell, with an equilibrium dissociation constant (KD) of 400 pmol/L. Erythropoietin, but not dimethylsulfoxide, induction caused a specific increase in receptor density to 3,300/cell on differentiating Rauscher cells. This is the first demonstration of membrane receptor regulation by erythropoietin that may be important in the complex interplay of hormonal effects during erythropoiesis.

Adenylyl Cyclases↗

PubMed1983

Erythropoietin-induced differentiation of Rauscher erythroleukemia cells.

We have shown morphologic and biochemical evidence for erythroid differentiation in the erythropoietin-responsive cell line Rauscher murine erythroleukemia. These cells synthesize adult and presumably embryonic hemoglobin in response to erythropoietin and dimethyl sulfoxide. Clear differences are observed in some clones between different inducers. The molecular basis for these differences, which may relate to differential modes of inducer action, must be clarified. These cells possess a functional beta-adrenergic receptor/adenylyl cyclase complex remarkably similar to that found on erythrocytes of several species. The receptor density is up-regulated specifically by erythropoietin and, as such, is the first description of membrane receptor regulation by this hormone. Thus, we now have the opportunity to investigate the development of the receptor-cyclase complex on the differentiating erythroid cell and to elucidate its role in the complex interplay of erythropoietin and other hormonal effects during erythropoiesis.

Animals↗

PubMed1981

Adenylate cyclase coupled beta adrenergic receptors of Rauscher erythroleukemia cells.

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1-Methyl-3-isobutylxanthine↗