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CLINICAL RESEARCH: AGING AND CARDIAC FUNCTION

Unchanged G-protein-coupled receptor kinase activity in the aging human heart

Kirsten Leineweber, PhD^*, Stefan Klapproth, BS^*, Anja Beilfuß^*, Rolf-Edgar Silber, MD, Gerd Heusch, MD, FACC^*, Thomas Philipp, MD^* and Otto-Erich Brodde, PhD^*,*

^* Departments of Pathophysiology and Nephrology, University of Essen School of Medicine, Essen, Germany
Clinic for Cardiothoracic Surgery, Martin-Luther-University of Halle-Wittenberg, Halle, Germany

Manuscript received April 10, 2003; accepted April 30, 2003.

^* Reprint requests and correspondence: Dr. Otto-Erich Brodde, Departments of Pathophysiology and Nephrology, University of Essen School of Medicine, Hufelandstrasse 55, D-45147 Essen, Germany.
otto-erich.brodde{at}uni-essen.de

OBJECTIVES: We sought to find out whether G-protein-coupled receptor kinase (GRK) activity is also increased in the aging human heart.

BACKGROUND: In the aging and failing human heart, cardiac beta-adrenoceptors (beta-AR) are desensitized. In heart failure (HF), an increase in cardiac GRK activity considerably contributes to this beta-AR desensitization.

METHODS: We assessed GRK activity (by in vitro rhodopsin phosphorylation) in the right atria (RA) from 16 children (mean age 9 ± 2 years) and 17 elderly patients (mean age 67 ± 2 years) without apparent HF and in the RA from four patients with end-stage HF.

RESULTS: Cytosolic and membranous GRK activities in the RA from children were not significantly different from those in elderly patients; in contrast, cytosolic and membranous GRK activities in the RA from patients with end-stage HF were significantly increased.

CONCLUSIONS: In contrast to the failing human heart, in the aging human heart, GRK activity is not increased. Thus, GRK activity appears to not play an important role in beta-AR desensitization in the aging human heart.

Abbreviations and Acronyms   AC = adenylyl cyclase   AR = adrenoceptor   ATP = adenosine triphosphate   cAMP = cyclic adenosine monophosphate   GRK = G-protein-coupled receptor kinase   GTP = guanosine triphosphate   HF = heart failure   NYHA = New York Heart Association   RA = right atria, right atrium

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