Insulin acts as an atypical KCNQ1/KCNE1‐current activator and reverses long QT in insulin‐resistant aged rats by accelerating the ventricular action potential repolarization through affecting the β 3 ‐adrenergic receptor signaling pathway

2021 ◽  
Author(s):  
Yusuf Olgar ◽  
Aysegul Durak ◽  
Ceylan V. Bitirim ◽  
Erkan Tuncay ◽  
Belma Turan
Keyword(s):  
Action Potential ◽  
Signaling Pathway ◽  
Adrenergic Receptor ◽  
Receptor Signaling ◽  
Aged Rats ◽  
Long Qt ◽  
Insulin Resistant ◽  
Receptor Signaling Pathway ◽  
Action Potential Repolarization ◽  
Ventricular Action Potential

scholarly journals Regulation of the β-Adrenergic Receptor Signaling Pathway in Sustained Ligand-Activated Preconditioning

2019 ◽  
Vol 369 (1) ◽  
pp. 37-46 ◽  
Author(s):  
L. E. See Hoe ◽  
S. R. Foster ◽  
L. Wendt ◽  
H. H. Patel ◽  
J. P. Headrick ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Adrenergic Receptor ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway

Abstract P328: β-Blockers Can Enhance Short-Term Receptor Sensitivity in Silico and in Vitro

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Robert Amanfu ◽  
Jeffrey Saucerman
Keyword(s):  
Signaling Pathway ◽  
Adrenergic Receptor ◽  
Acute Stress ◽  
Receptor Signaling ◽  
Receptor Model ◽  
Receptor Sensitivity ◽  
Binding Studies ◽  
Receptor Signaling Pathway ◽  
Β Blocker ◽  
Β Blockers

A key feature of heart failure is the chronic elevation of circulating catecholamines which desensitizes the β-adrenergic receptor signaling pathway, rendering patients incapable of increasing cardiac output in response to acute stress (eg. exercise). β-adrenergic receptor blockers (β-blockers) are commonly used to treat this condition, but precisely how they work is still controversial and poorly understood. Two opposing theories are that β-blockers work by 1) blocking the harmful consequences of chronic signaling or 2) paradoxically increasing receptor sensitivity. To investigate whether β-blockers function by increasing receptor sensitivity, we extended a published computational model of the β 1 -adrenergic receptor signaling pathway developed in our lab by using a ternary complex receptor module. This receptor model includes the spontaneous switching between the active and inactive conformations of the receptor that is crucial for accurate representation of β-blockers. Parameter values were determined from literature to model 11 agonists and 10 β-blockers. The new receptor model was validated against ligand binding studies and adenylyl cyclase assays from literature. Chronic and acute stresses were modeled as low and high (100X greater) concentrations of the agonist isoproterenol. Simulations indicate that when the β-blocker propranolol is present during chronic stress, cAMP levels are increased upon application of an acute stress, elevating intracellular calcium levels and contractility. This suggests that in addition to blocking the harmful consequences of chronic signaling, β-blockers may sensitize the response to acute stress. Preliminary data from calcium imaging experiments in isolated cardiac ventricular cells confirm this prediction. Simulations with a range of commonly used β-blockers indicate that individual drugs differ significantly in their ability to enhance receptor sensitivity. In addition, simulation of the Gly389Arg polymorphism suggests that the Arg389 variant has reduced sensitization to acute stress in the presence of propranolol. These simulations are a first step towards evaluating personalized β-blocker therapies with computational models.

scholarly journals The polymorphic deleted-form of the human α2B-adrenergic receptor and its wild-type counterpart display post-receptor signaling pathway differences in LLC-PK1 cells

2016 ◽  
Vol 57 (4) ◽  
pp. 292-295 ◽  
Author(s):  
Orthodoxia Mastrogianni ◽  
Pierre-Antoine Crassous ◽  
Georgios Karkoulias ◽  
Dimosthenis Lykouras ◽  
Stéphane Schaak ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Adrenergic Receptor ◽  
Receptor Signaling ◽  
Wild Type ◽  
Wild Type Counterpart ◽  
Receptor Signaling Pathway
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