TRANSFORMING GROWTH-FACTOR-BETA-1 MODULATES THE NUMBER OF BETA-ADRENERGIC RECEPTORS IN CARDIAC FIBROBLASTS

The effects of transforming growth factor β-1 on concentration of intracellular Ca2+ changes in the presence of isoproterenol were studied in cardiac fibroblasts. Transforming growth factor β-1 effect on cyclic-AMP production and ligand assay of β-adrenergic receptors were also examined. Production of cyclic-AMP in fibroblasts preincubated with transforming growth factor β-1 decreased compared with non-transforming growth factor β-1- treated fibroblasts in the presence of isoproterenol. An increase of intracellular Ca2+ concentration in the presence of isoproterenol was also inhibited in transforming growth factor β-1-treated fibroblasts. Islet- activating protein did not restore these reactions of transforming growth factor β-1. Concentration change of intracellular calcium under the treatment of transforming growth factor β-1 was unaffected by forskolin addition. Binding of [3H]CGP-12177 was decreased to 47% of control preincubated for 24 h with transforming growth factor β-1 in fibroblasts. Scatchard plots suggested a decrease in β-adrenergic receptor number without specific change in receptor affinity. These results suggested that transforming growth factor β-1 modulates the signal transduction through β- adrenergic receptor and intracellular Ca2+ concentration by regulating the number of receptor in fibroblasts. © 1993 Academic Press Limited.