title: Regulation of beta-adrenergic responses during in vitro differentiation of mouse erythroleukemia cells.
abstract: Dimethyl sulfoxide (DMSO)-induced erythroid differentiation of Friend mouse erythroleukemia (MEL) cells is associated with a marked transient modulation of catecholamine sensitivity. Within 24 h after induction and well before the onset of hemoglobin synthesis, we observed a 3-fold increase in beta-receptor density and a more than 10-fold increase in receptor-coupled cAMP formation. During the following 4 days, in parallel with the development of normoblast-like cells, receptor numbers returned to preinduction levels while catecholamine-dependent cAMP formation remained significantly elevated. Simultaneously, the apparent potency of the beta-adrenoceptor agonist isoprenaline increased 10-fold. Improved receptor-cyclase coupling is probably due to a major shift in the expression of Gi and Gs regulatory proteins. Bacterial toxin-mediated ADP-ribosylation of membrane proteins suggests that the dominating species in native cells is Gi (Gsa:Gia = 1.7). By contrast, Gs predominates in differentiated cells (Gsa:Gia = 1.8:1). Receptor-independent forskolin-stimulated cAMP formation showed a pronounced, albeit transient, decrease during differentiation. We suggest that these changes in cellular cAMP responses may be important for transient positive or negative cooperative interactions between hormones and growth factors in the course of erythroid cell development.
authors.affiliation: Department of Pharmacology, University of Bern, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Moudry
authors.forename: H
authors.initials: H
authors.lastname: Porzig
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D007399:Interphase / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology* / Q000503:physiopathology; D007942:Leukemia, Experimental / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol; D004121:Dimethyl Sulfoxide