Ectonucleoside triphosphate diphosphohydrolases and ecto-5′-nucleotidase in purinergic signaling: how the field developed and where we are now

Zimmermann, Herbert

doi:10.1007/s11302-020-09755-6

Cited by 50 publications

(37 citation statements)

References 99 publications

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“…ATP is an agonist for all seven P2X receptors and can bind to all eight P2Y receptors except to the P2Y6 receptor ( 12 – 14 ). UTP is an agonist of P2Y2, P2Y4 and P2Y11 ( 12 , 13 ). To obtain a hint regarding the receptors involved in the observed affects the non-selective P2 receptors antagonist PPADS was used.…”

Section: Discussionmentioning

confidence: 99%

“…P2X receptors function as ligand-gated ion channels. ATP is a native agonist for all seven P2X receptors ( 12 , 13 ). P2Y receptors are G-protein coupled receptors (GPCR).…”

Section: Introductionmentioning

confidence: 99%

“…ATP can bind to all eight P2Y receptors except to the P2Y6 receptor. UTP is a native agonist of P2Y2, P2Y4 and P2Y11 ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Purinergic Enhancement of Anti-Leishmanial Effector Functions of Neutrophil Granulocytes

Möller

Laskay

2021

Front. Immunol.

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Although macrophages are considered for host cells for the multiplication of Leishmania, recent studies indicate the important role of neutrophil granulocytes as host cells for these intracellular parasites. Neutrophils have been shown to be massively and rapidly recruited to the site of Leishmania infection where they represent the first cells to encounter the parasites. Exposure to ATP and UTP have been shown to enhance anti-Leishmania activity of macrophages and intralesional injection of UTP led to strongly reduced parasite load in vivo. Since the in vivo anti-leishmanial effect of extracellular UTP correlated with enhanced neutrophil recruitment and enhanced ROS production at the site of Leishmania infection we hypothesized that exposure to extracellular nucleotides can directly enhance the killing of Leishmania by neutrophils. Since purinergic signaling is an essential mechanism of neutrophil activation the aim of the present study was to assess whether purinergic exposure results in the activation of anti-leishmanial neutrophil functions and, therefore, represent an essential component of enhanced anti-leishmanial defense in leishmaniasis. We could show that exposure to ATP and UTP led to activation and enhanced CD11b expression of primary human neutrophils in vitro. Leishmania-induced ROS production was strongly enhanced by extracellular ATP and UTP. Importantly, exposure to ATP and UTP resulted in enhanced killing of Leishmania donovani by neutrophils. In addition, ATP strongly enhanced the secretion of IL-8 and IL-1β by Leishmania-exposed neutrophils. Our results suggest that signaling via the P2 receptor and phosphorylation of Erk1/2, Akt and p38 are involved in the purinergic enhancement of anti-leishmanial functions of neutrophils.

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Section: Discussionmentioning

confidence: 99%

“…P2X receptors function as ligand-gated ion channels. ATP is a native agonist for all seven P2X receptors ( 12 , 13 ). P2Y receptors are G-protein coupled receptors (GPCR).…”

Section: Introductionmentioning

confidence: 99%

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Purinergic Enhancement of Anti-Leishmanial Effector Functions of Neutrophil Granulocytes

Möller

Laskay

2021

Front. Immunol.

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“…Indeed, they are utilized intracellularly in the so called “purine salvage pathway” to reconstitute nucleosides and nucleotides, which are essential for the biological functions of cells [ 48 ]. A more detailed description of the properties and activities of all enzymes involved in ATP and ADO metabolism has recently been reported in [ 52 , 53 ].…”

Section: Enzymes and Other Mechanisms Generally Involved In The Turnover Of Extracellular Purinesmentioning

confidence: 99%

In Search of a Role for Extracellular Purine Enzymes in Bone Function

et al. 2021

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Bone is one of the major tissues that undergoes continuous remodeling throughout life, thus ensuring both organic body growth during development and protection of internal organs as well as repair of trauma during adulthood. Many endogenous substances contribute to bone homeostasis, including purines. Their role has increasingly emerged in recent decades as compounds which, by interacting with specific receptors, can help determine adequate responses of bone cells to physiological or pathological stimuli. Equally, it is recognized that the activity of purines is closely dependent on their interconversion or metabolic degradation ensured by a series of enzymes present at extracellular level as predominantly bound to the cell membrane or, also, as soluble isoforms. While the effects of purines mediated by their receptor interactions have sufficiently, even though not entirely, been characterized in many tissues including bone, those promoted by the extracellular enzymes providing for purine metabolism have not been. In this review, we will try to circumstantiate the presence and the role of these enzymes in bone to define their close relationship with purine activities in maintaining bone homeostasis in normal or pathological conditions.

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“…Nucleotide levels are regulated by ectonucleotidases, a group of enzymes constituted by nucleotide pyrophosphatases/phosphodiesterases (NPPs), nucleoside triphosphate diphosphohydrolases (NTPDases; CD39), alkaline phosphatase, and ecto-5′-nucleotidase (5′-NT, CD73; Bonan, 2012 ; Zimmermann, 2021 ). Ectonucleotidases promote the extracellular hydrolysis of ATP, producing ADP, adenosine monophosphate (AMP), and adenosine controlling their extracellular concentrations ( Burnstock, 1980 ; Bonan, 2012 ; Cheffer et al, 2018 ; Cieslak et al, 2019 ).…”

Section: Purinergic Signalingmentioning

confidence: 99%

Purinergic Signaling in the Pathophysiology and Treatment of Huntington’s Disease

Wiprich

Bonan

2021

Front. Neurosci.

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Huntington’s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder inherited in an autosomal dominant manner. This condition is characterized by motor dysfunction (chorea in the early stage, followed by bradykinesia, dystonia, and motor incoordination in the late stage), psychiatric disturbance, and cognitive decline. The neuropathological hallmark of HD is the pronounced neuronal loss in the striatum (caudate nucleus and putamen). The striatum is related to the movement control, flexibility, motivation, and learning and the purinergic signaling has an important role in the control of these events. Purinergic signaling involves the actions of purine nucleotides and nucleosides through the activation of P2 and P1 receptors, respectively. Extracellular nucleotide and nucleoside-metabolizing enzymes control the levels of these messengers, modulating the purinergic signaling. The striatum has a high expression of adenosine A2A receptors, which are involved in the neurodegeneration observed in HD. The P2X7 and P2Y2 receptors may also play a role in the pathophysiology of HD. Interestingly, nucleotide and nucleoside levels may be altered in HD animal models and humans with HD. This review presents several studies describing the relationship between purinergic signaling and HD, as well as the use of purinoceptors as pharmacological targets and biomarkers for this neurodegenerative disorder.

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Ectonucleoside triphosphate diphosphohydrolases and ecto-5′-nucleotidase in purinergic signaling: how the field developed and where we are now

Cited by 50 publications

References 99 publications

Purinergic Enhancement of Anti-Leishmanial Effector Functions of Neutrophil Granulocytes

Purinergic Enhancement of Anti-Leishmanial Effector Functions of Neutrophil Granulocytes

In Search of a Role for Extracellular Purine Enzymes in Bone Function

Purinergic Signaling in the Pathophysiology and Treatment of Huntington’s Disease

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