Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A<sub>2A</sub> and A<sub>2B</sub> receptor agonists

Wragg, Edward S; Pannucci, Patrizia; Hill, Stephen J.; Woolard, Jeanette; Cooper, Samantha

doi:10.1002/prp2.975

Cited by 3 publications

(1 citation statement)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, after the use of an A 2A R agonist, the increase in the heart rate was attenuated by a β-blocker. Thus, Wragg et al demonstrated a direct activation of the sympathetic nervous system by A 2A R stimulation [ 171 ].…”

Section: Association Between Atrial Fibrillation Risk Factors and The...mentioning

confidence: 99%

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

et al. 2022

View full text Add to dashboard Cite

Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative review is to report the most recent advances in the potential role of the adenosinergic system in the pathophysiology of AF. After a comprehensive approach describing adenosinergic system signaling and the mechanisms of the initiation and maintenance of AF, we address the interactions of the adenosinergic system’s signaling with AF. Indeed, adenosine release can activate four G-coupled membrane receptors, named A1, A2A, A2B and A3. Activation of the A2A receptors can promote the occurrence of delayed depolarization, while activation of the A1 receptors can shorten the action potential’s duration and induce the resting membrane’s potential hyperpolarization, which promote pulmonary vein firing, stabilize the AF rotors and allow for functional reentry. Moreover, the A2B receptors have been associated with atrial fibrosis homeostasis. Finally, the adenosinergic system can modulate the autonomous nervous system and is associated with AF risk factors. A question remains regarding adenosine release and the adenosine receptors’ activation and whether this would be a cause or consequence of AF.

show abstract

Section: Association Between Atrial Fibrillation Risk Factors and The...mentioning

confidence: 99%

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

et al. 2022

View full text Add to dashboard Cite

show abstract

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A_2A and A_2B receptor agonists

Wragg

Pannucci

Hill

et al. 2022

Pharmacology Res & Perspec

Self Cite

View full text Add to dashboard Cite

A2A and A2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A2A or A2B receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of β1‐ and β2‐adrenoceptors in mediating the different cardiovascular responses to selective A2A and A2B receptor stimulation. Hemodynamic variables were measured in conscious male Sprague‐Dawley rats (350–450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A2A‐selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg−1.min−1) or the A2B‐selective agonist BAY 60–6583 (4.0, 13.3, 40.0 µg.kg−1.min−1) in the absence or following pre‐treatment with the non‐selective β‐antagonist propranolol (1.0 mg.kg−1), the selective β1‐antagonist CGP 20712A (200 µg.kg−1), or the selective β2‐antagonist ICI 118,551 (2.0 mg.kg−1) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60–6583‐mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60–6583‐induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac β1‐adrenoceptors as a mechanism for the A2A‐ and A2B‐induced tachycardia. However, the regionally selective effects of A2B agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia.

show abstract

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists

Cullum,

Platt,

Dale

et al. 2024

Commun Biol

View full text Add to dashboard Cite

The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conformational states in the absence of ligands; an inactive R state and an active R* state that differ in their affinities for agonists, inverse agonists, and G-protein alpha subunits. The proportion of R* receptors that exist in the absence of agonists determines the level of constitutive receptor activity. In this study we demonstrate that mechanical stimulation can induce β2-adrenoceptor agonist-independent Gs-mediated cAMP signalling that is sensitive to inhibition by inverse agonists such as ICI-118551 and propranolol. The size of the mechano-sensitive response is dependent on the cell surface receptor expression level in HEK293G cells, is still observed in a ligand-binding deficient D113A mutant β2-adrenoceptor and can be attenuated by site-directed mutagenesis of the extracellular N-glycosylation sites on the N-terminus and second extracellular loop of the β2-adrenoceptor. Similar mechano-sensitive agonist-independent responses are observed in HEK293G cells overexpressing the A2A-adenosine receptor. These data provide new insights into how agonist-independent constitutive receptor activity can be enhanced by mechanical stimulation and regulated by inverse agonists.

show abstract

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A_2A and A_2B receptor agonists

Cited by 3 publications

References 63 publications

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A_2A and A_2B receptor agonists

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists

Contact Info

Product

Resources

About

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists

Cited by 3 publications

References 63 publications

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists

Contact Info

Product

Resources

About

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A_2A and A_2B receptor agonists

Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A_2A and A_2B receptor agonists