Beta-adrenergic regulation of camp and protein phosphorylation in wild-type and phospholamban-knockout mouse hearts. Kiss, Eva, Istvan Edes, Yoji Sato, Wusheng Luo, Stephen B. Liggett, and Evangelia G. Kranias. Departments of Pharmacology and Cell Biophysics and Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575 and Heart and Lung Department, Medical University of Debrecen, Debrecen, Hungary 4004
APStracts 3:0343H, 1996.
The stimulatory effects of [beta]-adrenergic agonists reflect increases in intracellular cAMP levels and phosphorylation of key regulatory proteins in the heart. One of these phosphoproteins is phospholamban in sarcoplasmic reticulum and ablation of phospholamban is associated with attenuation of the contractile responses to [beta]-adrenergic stimulation in the mouse heart. To determine whether this attenuation of [beta]-stimulation is due to altered phosphorylation characteristics of the other key cardiac phosphoproteins and/or to compensatory responses occurring in the absence of phospholamban, phospholamban-knockout and wild-type hearts were perfused and the protein phosphorylation patterns were examined. The [beta]-adrenergic receptor density, adenylyl cyclase activity, tissue cAMP levels and the basal phosphoprotein pattern were similar between phospholamban-knockout and wild-type hearts. Isoproterenol perfusion resulted in similar increases in the tissue cAMP-levels and the degree of phosphorylation of troponin I, C-protein and the 21 kDa microsomal protein in wild-type and phospholamban-knockout hearts. These findings indicate that the attenuation of isoproterenol -mediated increases in contractility of the phospholamban-knockout hearts is not due to alterations in the [beta]-adrenergic signal transduction pathway or the degree of phosphorylation of the key cardiac regulatory phosphoproteins in myofibrils and sarcolemma. 

Received 8 December 1995; accepted in final form 2 August 1996.
APS Manuscript Number H1139-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996