Transforming growth factor beta-1 attenuates endothelin-1-induced functions in neonatal cardiac myocytes

In the present study we characterized a "crosstalk" mechanism between transforming growth factor beta-1 (TGF β-1) and endothelin-1 (ET1) signaling pathways in neonatal cardiac myocytes. A 5 minute pretreatment with 1 ng/ml concentrations of TGF β-1 attenuated ET1-induced negative chronotropic effects and translocation of the α, δ and εPKC isozymes to the particulate cell fraction. We found no effect of TGF β-1 on responses induced by the P₂ purinergic agonist ATP or phorbol ester. Treatment of cardiac myocytes with acidic fibroblast growth factor (aFGF) did not alter ET1- or ATP-mediated effects on contraction rate or translocation of PKC isozymes to the particulate fraction. Our studies suggest that TGF β-1 may act as a negative modulator of ET1- but not ATP- or phorbol ester-induced PKC isozyme signaling events in neonatal cardiac myocytes. A better understanding of the complex ET1 and TGF β-1 signaling mechanisms in neonatal heart cells should enhance our knowledge regarding the interplay between these pathways.