cAMP concentrations, cAMP dependent protein kinase activity, and phospholamban in non-failing and failing myocardium.
OBJECTIVE
Several signal transduction defects such as a reduction of myocardial cAMP formation and an altered intracellular Ca2+ handling have been observed in the failing human myocardium. The aim of the study was to obtain data on changes beyond cAMP formation involving cAMP dependent protein kinase and its substrates.


METHODS
cAMP dependent protein kinase activity and cAMP concentrations were measured in the particulate and soluble fraction of failing human hearts (ischaemic, and dilated cardiomyopathy) and non-failing donor hearts. Phospholamban was quantified by cAMP dependent phosphorylation using 32P-ATP as substrate and on western blots using a monoclonal antibody.


RESULTS
cAMP concentrations were reduced in the particulate fraction in both ischaemic and dilated cardiomyopathy and in the soluble fraction in dilated cardiomyopathy, but there was no difference in cAMP dependent protein kinase activity. Both phospholamban levels and cAMP dependent phosphorylation of phospholamban were similar in non-failing myocardium and in both ischaemic and dilated cardiomyopathy.


CONCLUSIONS
These findings show that the reduction of cAMP formation is the predominant alteration in heart failure, but cAMP dependent protein kinase and phospholamban are evidently unchanged.
Klinik III für Innere Medizin, University of Cologne, Germany.
M
M
Böhm
B
B
Reiger
R H
RH
Schwinger
E
E
Erdmann
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000378:metabolism*; D000328:Adult; D001345:Autoradiography; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D002135:Calcium-Binding Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000099211:Phospholamban