Beta-adrenoceptor and adenylate cyclase regulation in cardiac myocyte growth

We studied the effect of growth on beta-adrenergic receptor properties of neonatal rat heart myocytes cultured in serum-free medium with transferrin and insulin. Growth was induced by addition of 1 microM (-)-norepinephrine for two days, 200 nM of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for two days, or 30 nM T3 for six days. The Kd values for beta-receptor binding (125I-ICYP) were unaffected by growth. The maximum number of beta-receptor binding sites calculated as sites/cell was increased 1.47-fold by T3 (p less than .005), but was decreased to 54% of control values by (-)-norepinephrine (p less than .005): TPA had no effect on either Kd or Bmax values. (-)-Isoproterenol-stimulated adenylate cyclase activity was augmented only in membranes from T3-treated cells and was reduced by 69% in membranes from (-)-norepinephrine treated cells. TPA had no effect on (-)-isoproterenol-stimulated adenylate cyclase activity. We conclude that the mechanisms controlling beta-adrenergic receptor number may be distinct from those controlling growth, since receptor number does not correlate with cell enlargement. Furthermore, in (-)-norepinephrine-stimulated growth, which we have shown previously is an alpha 1-adrenoceptor mediated response, beta-adrenergic signal transduction is modulated in a directionally opposite fashion.