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.