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.
Moudry
R
R
Pharmakologisches Institut, Universität Bern, Switzerland.
Porzig
H
H
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005622:Friend murine leukemia virus; D019204:GTP-Binding Proteins / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D010869:Pindolol; D011065:Poly(ADP-ribose) Polymerases; D019204:GTP-Binding Proteins; D004121:Dimethyl Sulfoxide