Age-related β-adrenergic receptor-mediated vasorelaxation is changed by altering G protein receptor kinase 2 expression

2011 ◽  
Vol 55 (5-6) ◽  
pp. 178-188 ◽  
Author(s):  
William E. Schutzer ◽  
Hong Xue ◽  
John Reed ◽  
Terry Oyama ◽  
Douglas R. Beard ◽  
...  
Keyword(s):  
G Protein ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
Age Related ◽  
Protein Receptor

Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation

2007 ◽  
Vol 293 (3) ◽  
pp. H1596-H1603 ◽  
Author(s):  
Dario Leosco ◽  
Giuseppe Rengo ◽  
Guido Iaccarino ◽  
Amelia Filippelli ◽  
Anastasios Lymperopoulos ◽  
...  
Keyword(s):  
Exercise Training ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Favorable Effect ◽  
Control Group ◽  
Receptor Kinase ◽  
Protein Receptor ◽  
Wistar Kyoto

Cardiac β-adrenergic receptor (β-AR) signaling and left ventricular (LV) responses to β-AR stimulation are impaired with aging. It is shown that exercise and β-AR blockade have a favorable effect on cardiac and vascular β-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on β-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg·kg−1·day−1 for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to β-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane β-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac β-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of β-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and β-AR blockade can similarly ameliorate β-AR signaling in the aged heart, leading to improved β-AR responsiveness and corresponding LV inotropic reserve.

AGONIST ACTIVATED ADRENOCORTICOTROPIN RECEPTOR INTERNALIZES VIA A CLATHRIN-MEDIATED G PROTEIN RECEPTOR KINASE DEPENDENT MECHANISM

2002 ◽  
Vol 28 (4) ◽  
pp. 281-289 ◽  
Author(s):  
A. H. Baig ◽  
F. M. Swords ◽  
M. Szaszák ◽  
P. J. King ◽  
L. Hunyady ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Kinase ◽  
Protein Receptor ◽  
Dependent Mechanism

Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction

2021 ◽  
Author(s):  
Thomas Pilgrim ◽  
René Vollenbroich ◽  
Sarah Deckarm ◽  
Christoph Gräni ◽  
Stephan Dobner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
G Protein ◽  
Receptor Kinase ◽  
Anterior Myocardial Infarction ◽  
Protein Receptor

Upregulation of G protein-linked receptor kinases with advancing age in rat aorta

2001 ◽  
Vol 280 (3) ◽  
pp. R897-R903 ◽  
Author(s):  
William E. Schutzer ◽  
John F. Reed ◽  
Michael Bliziotes ◽  
Scott L. Mader
Keyword(s):  
G Protein ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Fischer 344 Rats ◽  
Membrane Expression ◽  
Fischer 344 ◽  
Age Related ◽  
Protein Receptor ◽  
Receptor Kinases ◽  
Increased Activity

The age-related decline in β-adrenergic receptor (β-AR)-mediated vasorelaxation is associated with desensitization of β-ARs without significant downregulation. The primary mode of this homologous β-AR desensitization, in general, is via G protein receptor kinases (GRK). Therefore, we hypothesize that age-related changes in GRKs are causative to this etiology in rat aorta. Herein, we investigate the activity and cellular distribution (cytoplasmic vs. membrane) of several GRK isoforms and β-arrestin proteins. GRK activity was assessed in extracts from aortic tissue of 6-wk, 6-mo, 12-mo, and 24-mo-old male Fischer-344 rats using a rhodopsin phosphorylation assay. We also performed immunoblots on lysates from aorta with specific antibodies to GRK-2, -3, -5, and β-arrestin-1. Results show an age-related increase in GRK activity. Furthermore, expression of GRK-2 (cytoplasmic and membrane), GRK-3 (cytoplasmic and membrane), and β-arrestin (soluble) increased with advancing age, whereas GRK-5 (membrane) expression remained unchanged. These results suggest that age is associated with increased activity and expression of specific GRKs. This increase likely results in enhanced phosphorylation and desensitization of β-ARs. These biochemical changes are consistent with observed aging physiology.

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