scholarly journals β-Adrenergic receptor desensitization in man: insight into post-exercise attenuation of cardiac function

2006 ◽  
Vol 577 (2) ◽  
pp. 717-725 ◽  
Author(s):  
Emma Hart ◽  
Ellen Dawson ◽  
Peter Rasmussen ◽  
Keith George ◽  
Niels H. Secher ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Receptor Desensitization ◽  
Post Exercise ◽  
Insight Into

β-Adrenergic receptor desensitization stimulates glucose uptake in C6 rat glioma cells

1982 ◽  
Vol 109 (3) ◽  
pp. 753-761 ◽  
Author(s):  
Nabuyuki Shitara ◽  
Paul E. McKeever ◽  
Craig Cummins ◽  
Barry H. Smith ◽  
Paul L. Kornblith ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Adrenergic Receptor ◽  
Glioma Cells ◽  
Receptor Desensitization ◽  
Rat Glioma

Abstract 339: Long-term AAV6-βARKct Myocardial Gene Therapy Improves Cardiac Function Via Restoration Of β-Adrenergic Receptor Signaling And Neurohormonal Status Of The Failing Heart

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Giuseppe Rengo ◽  
Anastasios Lymperopoulos ◽  
Carmela Zincarelli ◽  
Maria Donniacuo ◽  
Stephen Soltys ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Weight Ratio ◽  
Intramyocardial Injection ◽  
Molecular Abnormalities ◽  
Virus Serotype

BACKGROUND: The up-regulation of G protein-coupled receptor kinase-2 (GRK2) that is present in compromised myocardium contributes to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function in heart failure (HF). The peptide βARKct, which inhibits the activation of GRK2, has been shown in acute gene transfer experiments to rescue HF. This study was designed to evaluate chronic βARKct expression in post-myocardial infarction (MI) induced HF using stable myocardial gene delivery with adeno-associated virus serotype-6 (AAV6). METHODS AND RESULTS: In 12 week post-MI HF rats, we delivered βARKct or as a control, Green Fluorescent Protein, via direct intramyocardial injection. We also treated groups with concurrent administration of metoprolol. We found robust and long-lasting (up to 12 weeks post-delivery) transgene expression in the left ventricle (LV) and βARKct expression resulted in significantly improved global heart function as LV ejection fraction and ±dP/dt were increased, whereas LV end diastolic diameter and pressure were decreased. At the molecular level, cardiac βAR density and cAMP accumulation significantly improved over control groups. Fibrotic and hypertrophy markers, as well as heart-to-body weight ratio were markedly decreased by βARKct gene therapy indicating active reversal of adverse LV remodeling. For the first time, we found that chronic βARKct expression and normalization of cardiac βAR signaling led to a reduction of circulating levels of cardiotoxic neurohormones (catecholamines and aldosterone) demonstrating a potential additive mechanism of GRK2 inhibition. Concomitant metoprolol administration preserved the gain in inotropy achieved by βARKct, suggesting compatibility of these two therapeutic modalities, however, metoprolol alone only prevented the deterioration of cardiac function in HF. CONCLUSIONS : Chronic cardiac βARKct gene therapy for HF treatment via AAV6-mediated intracardiac gene delivery is feasible and results in improved cardiac function accompanied by restoration of βAR molecular abnormalities and amelioration of neurohormonal status of HF. These findings suggest βARKct gene therapy might be clinically applicable and of significant value for human HF treatment. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

Cardiopulmonary bypass induces physiologic beta-adrenergic receptor desensitization

1992 ◽  
Vol 77 (Supplement) ◽  
pp. A660 ◽  
Author(s):  
n. Spah ◽  
P E Frasco ◽  
R L Smith ◽  
C Bowens ◽  
R L McRae ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Adrenergic Receptor ◽  
Receptor Desensitization ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic

scholarly journals Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications

2015 ◽  
Vol 62 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Joseph A. Giovannitti ◽  
Sean M. Thoms ◽  
James J. Crawford
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Adrenergic Receptor ◽  
Historical Perspective ◽  
Drug Class ◽  
Clinical Applications ◽  
Receptor Agonists ◽  
Panic Disorders ◽  
Hyperactivity Disorder ◽  
Cigarette Craving ◽  
Insight Into

Abstract The α-2 adrenergic receptor agonists have been used for decades to treat common medical conditions such as hypertension; attention-deficit/hyperactivity disorder; various pain and panic disorders; symptoms of opioid, benzodiazepine, and alcohol withdrawal; and cigarette craving.1 However, in more recent years, these drugs have been used as adjuncts for sedation and to reduce anesthetic requirements. This review will provide an historical perspective of this drug class, an understanding of pharmacological mechanisms, and an insight into current applications in clinical anesthesiology.

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