[The role of G protein, protein kinase C and Na(+)-H+ exchanger in endothelin-1-induced cardiomyocyte hypertrophic responses].
Endothelin-1 (ET-1) has been shown to be a potent growth factor and to induce cardiac hypertrophy. In the present study, we examined the role of G protein, protein kinase C (PKC) and Na(+)-H+ exchanger in ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes. ET-1 (10(-10)-10(-7) mol/L) induced promotion of 3H-leucine incorporation, increase in cell protein content and cell surface area in a dose-dependent manner with EC50 value of 5.2 x 10(-10), 5.2 x 10(-10) and 7.3 x 10(-10) mol/L respectively. All of these ET-1-induced cardiomyocyte hypertrophic responses were completely blocked by pretreatment with staurosporine (2 nmol/L), a protein kinase C inhibitor, and stimulated by 4-phorbol, 12-myristate, 13-acetate (PMA) (10(-8)-10(-6) mol/L), a protein kinase C activator, in a dose-dependent manner. Pretreatment of amiloride (10(-4) mol/L), a Na(+)-H+ exchange inhibitor completely inhibited the ET-1-induced, but not PMA-induced cardiomyocyte hypertrophic responses. The ET-1-induced increase in cardiomyocyte protein synthesis and cell surface area was significantly inhibited by pretreatment with pertussis toxin (150 ng/ml). These results suggest that ET-1-induced cardiomyocyte hypertrophy was linked with pertussis toxin sensitive G protein, and PKC and Na(+)-H+ exchange may be an important intracellular signaling transduction pathway during ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes.
Wu
B
B
Department of Physiology, Sun Yat-Sen University of Medical Sciences, Guangzhou 510089.
Wang
T H
TH
Pan
J Y
JY
Zhu
X N
XN
Zhan
C Y
CY
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000503:physiopathology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D009206:Myocardium / Q000473:pathology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate
D019332:Endothelin-1; D017923:Sodium-Hydrogen Exchangers; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate