Cyclic GMP-mediated phospholamban phosphorylation in intact cardiomyocytes.
The cGMP-mediated phospholamban phosphorylation was investigated in cardiomyocytes in response to receptor-dependent (atrial natriuretic peptide, ANP) and -independent (sodium nitroprusside; SNP) cGMP generation. ANP (1 nM-1 microM) induced phospholamban phosphorylation in a concentration-dependent fashion (EC50: 5.0 +/- 0.09 nM). Concomitantly, an elevation in cGMP levels was observed. Phospholamban was also dose-dependently phosphorylated in response to SNP, but it required about three orders of magnitude higher concentrations (EC50: 2.9 +/- 0.03 microM) than ANP. Treatment of the cells with 8Br-cGMP (10 microM) or with the specific activator of cGMP-protein kinase 8-pCPT-cGMP (1-100 microM) mimicked these effects. The results demonstrate for the first time that a ANP/cGMP signaling pathway exists in neonatal cardiomyocytes which may contribute to modulation of heart contractility.
Sabine
B
B
Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
Willenbrock
R
R
Haase
H
H
Karczewski
P
P
Wallukat
G
G
Dietz
R
R
Krause
E G
EG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D000099211:Phospholamban
D009320:Atrial Natriuretic Factor; D002135:Calcium-Binding Proteins; D006152:Cyclic GMP; D007545:Isoproterenol; D009599:Nitroprusside; D000099211:Phospholamban