Activation of cyclic AMP-dependent protein kinase in cardiomyocytes by anti-beta 1-adrenoceptor autoantibodies from patients with idiopathic dilated cardiomyopathy.
The serum of patients with idiopathic dilated cardiomyopathy contains agonistic autoantibodies that bind to beta 1-adrenoceptor and exert a positive chronotropic effect in cultured neonatal rat cardiomyocytes. In this study it is shown that these antibodies like isoproterenol increase the activity of cyclic AMP-dependent protein kinase (PKA) in the challenged myocytes. Cytosolic and particulate PKA activity was found to be increased as indicated by a rise in the PKA activity ratio from control values of 0.20 +/- 0.02 to 0.33 +/- 0.03 (p < 0.001), respectively, after exposure to the autoantibodies. Increases in PKA activity ratio by the autoantibodies as well as by isoproterenol were blocked in the presence of (-) propranolol. These findings complete the pathway by which the autoantibodies realize their chronotropic effects via beta-adrenoceptor-binding, cyclic AMP generation and activation of particulate and cytosolic cyclic AMP-dependent protein kinase.
Krause
E G
EG
Max Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany.
Bartel
S
S
Beyerdörfer
I
I
Wallukat
G
G
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000276:immunology*
D001323:Autoantibodies; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases