The beta-adrenergic receptor adenylate cyclase complex of Rauscher murine
erythroleukemia cells and its response to erythropoietin-induced
differentiation
AJ Sytkowski and CJ Kessler
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.
Volume 64,
Issue 1,
pp. 84-90,
07/01/1984
Copyright © 1984 by The American Society of Hematology
