Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

Ho, Ming‐Fen; Low, Leanne M.; Rose’Meyer, Roselyn Barbara

doi:10.1371/journal.pone.0150021

Cited by 17 publications

(14 citation statements)

References 40 publications

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“…In hypertensive patients adenosine activates the vascular renin-angiotensin system. P1R agonists have been suggested for the treatment of hypertension ( Ho M.F. et al, 2016 ).…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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“…In hypertensive patients adenosine activates the vascular renin-angiotensin system. P1R agonists have been suggested for the treatment of hypertension ( Ho M.F. et al, 2016 ).…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…Both adenosine and the selective A 2A R agonist produce concentration-dependent relaxation of coronary arteries isolated from control rats via activation of Kv 7 channels but not hypertensive rats [ 43 ]. There is downregulation of A 3 R expression and the A 3 R-mediated coronary vasodilation in perfused hearts from spontaneously hypertensive rats [ 38 ]. In hypertensive swine, the transmural spatial density of microvessels is twice as much as in normotensive animals, and myocardial levels and expression of endothelium-derived growth factors, e.g., FGF (in vascular smooth muscle cells and myocytes) and VEGF (in endothelial cells) are significantly increased.…”

Section: Introductionmentioning

confidence: 99%

Adenosine and adenosine receptor-mediated action in coronary microcirculation

et al. 2021

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Adenosine is an ubiquitous extracellular signaling molecule and plays a fundamental role in the regulation of coronary microcirculation through activation of adenosine receptors (ARs). Adenosine is regulated by various enzymes and nucleoside transporters for its balance between intra- and extracellular compartments. Adenosine-mediated coronary microvascular tone and reactive hyperemia are through receptors mainly involving A2AR activation on both endothelial and smooth muscle cells, but also involving interaction among other ARs. Activation of ARs further stimulates downstream targets of H2O2, KATP, KV and KCa2+ channels leading to coronary vasodilation. An altered adenosine-ARs signaling in coronary microcirculation has been observed in several cardiovascular diseases including hypertension, diabetes, atherosclerosis and ischemic heart disease. Adenosine as a metabolite and its receptors have been studied for its both therapeutic and diagnostic abilities. The present review summarizes important aspects of adenosine metabolism and AR-mediated actions in the coronary microcirculation.

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“…This response may not be due to the contribution of not only endothelium K ATP but also smooth muscle in vasodilation induced by adenosine receptor when activated by ATP after ATP degraded to adenosine (Ho, Low, & Rose'Meyer, 2016).…”

Section: Discussionmentioning

confidence: 92%

The Effects of Glycerl Trinitrate and Adenosine 5-Triphosphate on Activation of Potassium Channel-Mediated Vasorelaxation in Female rats aortic Smooth Muscle.

Al-Habib

Mohammed

2016

SJUOZ

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ABSTRACT:Nitric oxide (NO) is produced from virtually all cell types composing the cardiovascular tissue and regulates vascular function through fine regulation of excitation-contraction coupling. Endogenous metabolites play a major role in coronary autoregulation. Therefore, the aim of the present study is to investigate the contribution of Glyceryl trinitrate (GTN) and Adenosine 5-triphosphate (ATP) mediated relaxation in rat aortic smooth muscle in intact and endothelium denuded endothelium rings precontracted with Phenylephrine (PE). The thoracic aorta was isolated, cut into rings, and mounted in organ-bath chambers and isometric tension was recorded using PowerLab Data Acquisition System (Model ML 870). The results showed that GTN as NO donor produced dose-dependent relaxation in intact aortic rings precontracted with PE (1 µM) that disinhibited in the presence of Glibenclamide (GLIB), while GLIB attenuate the response induced by ATP in intact aortic rings. L-nitroarginine methylester (L-NAME) an antagonist for nitric oxide synthases (NOS), not abolish the response induced by GTN (Emax 55.28% ± 0.18). Caffeine, ATP receptors antagonist, were partially inhibit the relaxation induced by ATP (vasodilation rate decreased by about 20.57 %). In endothelium denuded aortic rings, vasorelaxation induced by ATP were significantly attenuated , while GTN significantly increased relaxation by removing endothelium. These results suggested that (1) ATP-dependent potassium channel did not involve in GTN inducing vasorelaxation while K ATP and A 2B receptors have a role in ATP mediated vasorelation (2) ATP partially dependent on endothelium in contrast to NO donors that independent to endothelium.

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Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

Cited by 17 publications

References 40 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Adenosine and adenosine receptor-mediated action in coronary microcirculation

The Effects of Glycerl Trinitrate and Adenosine 5-Triphosphate on Activation of Potassium Channel-Mediated Vasorelaxation in Female rats aortic Smooth Muscle.

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