Reduced number and coupling of beta-adrenergic receptors in a modified S49 mouse lymphoma cell line

Long-term culture of S49 wild-type cells in medium containing a high concentration of fetal calf serum leads to a modified (S49m) cell line with a reduced number of beta-adrenergic receptors (R). These S49m cells with a higher rate of proliferation were unable to respond to the beta-adrenergic agonists isoproterenol (ISO) and epinephrine as analysed by measuring adenylate cyclase (ac) activity on purified membranes of these cells. Additionally, no accumulation of cyclic AMP was obtained on S49m intact cells upon stimulation with beta-agonists. Nevertheless, S49m cells were able to respond significantly to the direct activation of the stimulatory guanine nucleotide binding (Gs) protein by aluminium tetrafluoride and sodium fluoride, and to the stimulation of another receptor coupled to the ac system through a Gs protein, by prostaglandin E1 (PGE1). When cloning S49m cells, similar results were obtained upon stimulation with ISO and PGE1 and the cloned cells express the same thy 1.2 and class Id molecules as do S49 cells. The study of S49m cells indicates that they are a beta-adrenergic R-deficient variant distinct from the other variants described for S49 cells.