Transforming growth factor beta-1 modulates the number of beta-adrenergic receptors in cardiac fibroblasts.
The effects of transforming growth factor beta-1 on concentration of intracellular Ca2+ changes in the presence of isoproterenol were studied in cardiac fibroblasts. Transforming growth factor beta-1 effect on cyclic-AMP production and ligand assay of beta-adrenergic receptors were also examined. Production of cyclic-AMP in fibroblasts preincubated with transforming growth factor beta-1 decreased compared with non-transforming growth factor beta-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 beta-1-treated fibroblasts. Islet-activating protein did not restore these reactions of transforming growth factor beta-1. Concentration change of intracellular calcium under the treatment of transforming growth factor beta-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 beta-1 in fibroblasts. Scatchard plots suggested a decrease in beta-adrenergic receptor number without specific change in receptor affinity. These results suggested that transforming growth factor beta-1 modulates the signal transduction through beta-adrenergic receptor and intracellular Ca2+ concentration by regulating the number of receptor in fibroblasts.
Iizuka
K
K
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Sano
H
H
Kawaguchi
H
H
Kitabatake
A
A
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D005347:Fibroblasts / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D016212:Transforming Growth Factor beta; D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium