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 beta-1) and endothelin-1 (ET1) signaling pathways in neonatal cardiac myocytes. A 5 minute pretreatment with 1 ng/ml concentrations of TGF beta-1 attenuated ET1-induced negative chronotropic effects and translocation of the alpha, delta and varepsilonPKC isozymes to the particulate cell fraction. We found no effect of TGF beta-1 on responses induced by the P(2) 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 beta-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 beta-1 signaling mechanisms in neonatal heart cells should enhance our knowledge regarding the interplay between these pathways.
Johnson
John A
JA
The Department of Pharmacology and Toxicology, School of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912-2300, USA. jjohnson@mail.mcg.edu
Waller
Jennifer
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001345:Autoradiography; D015153:Blotting, Western; D003720:Densitometry; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D019332:Endothelin-1; D007527:Isoenzymes; D010703:Phorbol Esters; D018048:Receptors, Purinergic P2; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016220:Fibroblast Growth Factor 1; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate