Extracellular nucleotide and nucleoside signaling in vascular and blood disease

Idzko, Marco; Ferrari, Davide; Riegel, Ann-Kathrin; Eltzschig, Holger K.

doi:10.1182/blood-2013-09-402560

Cited by 122 publications

(112 citation statements)

References 111 publications

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“…General schemes of purine-converting pathways include nucleoside triphosphate diphosphohydrolase-1 (NTPDase1, also known as CD39), other enzymes of NTPDase and nucleotide pyrophosphatase/phosphodiesterase families, ecto-5′-nucleotidase/CD73 (eN/CD73), alkaline phosphatases, adenosine deaminase, and backward ATP-regenerating enzymes adenylate kinase (AK) and nucleoside diphosphate kinase (NDPK) [19,21,22]. Research over the past decade highlights the central role for CD39-CD73 axis in controlling the balance between ATP, ADP, and adenosine in a wide range of diseases, including endothelial barrier dysfunction and activation and aggregation of platelets at sites of vascular injury, hypoxia, and inflammation [20,23,24]. However, current knowledge of regulatory pathways governing the duration and magnitude of purinergic signaling in the eye remains rather scattered.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

et al. 2016

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“…1,2,7,8,11,12,35) Previous studies have reported that the application of these substances results in vasoconstriction or vasodilatation and that the extent of these responses is altered in hypertensive arteries. 1,2,11,29) However, few studies have compared the vasorelaxant effect of these three substances in the same region of arteries from hypertensive subjects.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10] They also exert a variety of effects on the vasculature, such as platelet activation and alteration in smooth muscle contraction and relaxation, by activating plasmalemmal receptors (e.g., purinoceptors). 1,2,8,11,12) Purinoceptors are classified into two subtypes, namely P1 and P2, based on their pharmacological properties and molecular cloning characteristics.…”

mentioning

confidence: 99%

A Comparative Study of Vasorelaxant Effects of ATP, ADP, and Adenosine on the Superior Mesenteric Artery of SHR

Watanabe

Matsumoto

Ando

et al. 2016

Biological & Pharmaceutical Bulletin

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We investigated superior mesenteric arteries from spontaneously hypertensive rats (SHR) to determine the relaxation responses induced by ATP, ADP, and adenosine and the relationship between the relaxant effects of these compounds and nitric oxide (NO) or cyclooxygenase (COX)-derived prostanoids. In rat superior mesenteric artery, relaxation induced by ATP and ADP but not by adenosine was completely eliminated by endothelial denudation. In the superior mesenteric arteries isolated from SHR [vs. age-matched control Wistar Kyoto rats (WKY)], a) ATP-and ADP-induced relaxations were weaker, whereas adenosine-induced relaxation was similar in both groups, b) ATP-and ADP-induced relaxations were substantially and partly reduced by N G -nitro-L-arginine [a NO synthase (NOS) inhibitor], respectively, c) indomethacin, an inhibitor of COX, increased ATP-and ADP-induced relaxations, d) ADP-induced relaxation was weaker under combined inhibition by NOS and COX, and e) adenosine-induced relaxation was not altered by treatment with these inhibitors. These data indicate that levels of responsiveness to these nucleotides/adenosine vary in the superior mesenteric arteries from SHR and WKY and are differentially modulated by NO and COX-derived prostanoids.Key words adenosine; ADP; ATP; relaxation; spontaneously hypertensive rat Extracellular nucleotides and their metabolites including ATP, ADP, and adenosine play pivotal roles in (patho)-physiological processes, including immune responses, inflammation, cardiac fibrosis, atherosclerosis, hypertension, and diabetes.1-10) They also exert a variety of effects on the vasculature, such as platelet activation and alteration in smooth muscle contraction and relaxation, by activating plasmalemmal receptors (e.g., purinoceptors). 1,2,8,11,12) Purinoceptors are classified into two subtypes, namely P1 and P2, based on their pharmacological properties and molecular cloning characteristics.11,12) Adenosine and its phosphates ATP and ADP are endogenous ligands for P1 and P2 receptors, respectively. Several studies have suggested that the expression and signaling responses of these receptors is altered under disease conditions. 4,11,[13][14][15][16][17] Moreover, these receptors can mediate a variety of responses to several nucleotides, resulting in the existence of multiple receptors with overlapping ligand preferences. 11,18)Therefore, it is difficult to understand the effect of nucleotides on vascular function under pathophysiological conditions. Hypertension is a leading risk factor for cardiovascularassociated morbidity and mortality. An important and contributory element in sustained hypertension is an increase in vascular tone, potentially resulting from concurrently reduced relaxation and augmented contraction induced by various endogenous ligands. [19][20][21][22][23][24][25][26] Hypertension-associated vascular dysfunction is partly regulated by endothelium-derived factors. [21][22][23][24] There is a fine balance between endothelium-derived relaxing and contracting factors, a disturba...

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“…Extracellular nucleotides such as ATP, ADP, and AMP, and their nucleoside derivative adenosine, are signaling compounds involved in several biological processes, including inflammation and immune responses [16]. While ATP acts as a Bfind-me signal^that conducts phagocytes to inflammatory sites, its breakdown product adenosine contributes to the engineering of inflammation and immune responses by providing a suppressive tissueprotecting signal [17].…”

Section: Introductionmentioning

confidence: 99%

Adenosine reduces reactive oxygen species and interleukin-8 production by Trichomonas vaginalis-stimulated neutrophils

Frasson

Menezes

Goelzer

et al. 2017

Purinergic Signalling

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Trichomonas vaginalis is a flagellated protozoan that affects the human urogenital tract causing 276.4 million new infections a year. The parasite elicits a vaginal mucosal infiltration of immune cells, especially neutrophils which are considered to be primarily responsible for cytological change observed at the infection site as well as the major contributor in the inflammatory response against the parasite. Extracellular nucleotides and their nucleosides are signaling compounds involved in several biological processes, including inflammation and immune responses. Once in the extracellular space, the nucleotides and nucleosides can directly activate the purinergic receptors. Herein, we investigated the involvement of purinergic signaling on the production of reactive oxygen species (ROS) and cytokines by T. vaginalis-stimulated neutrophils. Parasites were able to induce an increase in ROS and IL-8 levels while they did not promote IL-6 secretion or neutrophil elastase activity. Adenine and guanine nucleotides or nucleosides were not able to modulate ROS and cytokine production; however, when T. vaginalis-stimulated neutrophils were incubated with adenosine and adenosine deaminase inhibitor, the levels of ROS and IL-8 were significantly reduced. These immunosuppressive effects were probably a response to the higher bioavailability of adenosine found in the supernatant as result of inhibition of enzyme activity. The involvement of P1 receptors was investigated by immunofluorescence and A1 receptor was the most abundant. Our data show that the influence of purinergic signaling, specifically those effects associated with adenosine accumulation, on the modulation of production of proinflammatory mediators by T. vaginalis-stimulated neutrophils contribute to the understanding of immunological aspects of trichomoniasis.

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Extracellular nucleotide and nucleoside signaling in vascular and blood disease

Cited by 122 publications

References 111 publications

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

A Comparative Study of Vasorelaxant Effects of ATP, ADP, and Adenosine on the Superior Mesenteric Artery of SHR

Adenosine reduces reactive oxygen species and interleukin-8 production by Trichomonas vaginalis-stimulated neutrophils

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