scholarly journals The Biochemical Properties of the Arabidopsis Ecto-Nucleoside Triphosphate Diphosphohydrolase AtAPY1 Contradict a Direct Role in Purinergic Signaling

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0115832 ◽  
Author(s):  
Carolin Massalski ◽  
Jeannine Bloch ◽  
Matthias Zebisch ◽  
Iris Steinebrunner
Keyword(s):  
Purinergic Signaling ◽  
Biochemical Properties ◽  
Nucleoside Triphosphate ◽  
Direct Role ◽  
Nucleoside Triphosphate Diphosphohydrolase

scholarly journals Coexpression of ecto-5′-nucleotidase/CD73 with specific NTPDases differentially regulates adenosine formation in the rat liver

2012 ◽  
Vol 302 (4) ◽  
pp. G447-G459 ◽  
Author(s):  
Michel Fausther ◽  
Joanna Lecka ◽  
Elwy Soliman ◽  
Gilles Kauffenstein ◽  
Julie Pelletier ◽  
...  
Keyword(s):  
Rat Liver ◽  
Vascular Endothelial Cells ◽  
Purinergic Signaling ◽  
Biochemical Properties ◽  
Nucleoside Triphosphate ◽  
Protein Levels ◽  
Nucleoside Triphosphate Diphosphohydrolase ◽  
Normal Rat ◽  
Portal Fibroblasts ◽  
The Impact

Ectonucleotidases modulate purinergic signaling by hydrolyzing ATP to adenosine. Here we characterized the impact of the cellular distribution of hepatic ectonucleotidases, namely nucleoside triphosphate diphosphohydrolase (NTPDase)1/CD39, NTPDase2/CD39L1, NTPDase8, and ecto-5′-nucleotidase/CD73, and of their specific biochemical properties, on the levels of P1 and P2 receptor agonists, with an emphasis on adenosine-producing CD73. Immunostaining and enzyme histochemistry showed that the distribution of CD73 (protein and AMPase activity) overlaps partially with those of NTPDase1, -2, and -8 (protein levels and ATPase and ADPase activities) in normal rat liver. CD73 is expressed in fibroblastic cells located underneath vascular endothelial cells and smooth muscle cells, which both express NTPDase1, in portal spaces in a distinct fibroblast population next to NTPDase2-positive portal fibroblasts, and in bile canaliculi, together with NTPDase8. In fibrotic rat livers, CD73 protein expression and activity are redistributed but still overlap with the NTPDases mentioned. The ability of the observed combinations of ectonucleotidases to generate adenosine over time was evaluated by reverse-phase HPLC with the recombinant rat enzymes at high “inflammatory” (500 μM) and low “physiological” (1 μM) ATP concentrations. Overall, ATP was rapidly converted to adenosine by the NTPDase1+CD73 combination, but not by the NTPDase2+CD73 combination. In the presence of NTPDase8 and CD73, ATP was sequentially dephosphorylated to the CD73 inhibitor ADP, and then to AMP, thus resulting in a delayed formation of adenosine. In conclusion, the specific cellular cocompartmentalization of CD73 with hepatic NTPDases is not redundant and may lead to the differential activation of P1 and P2 receptors, under normal and fibrotic conditions.

scholarly journals NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 147
Author(s):  
Romuald Brice Babou Kammoe ◽  
Gilles Kauffenstein ◽  
Julie Pelletier ◽  
Bernard Robaye ◽  
Jean Sévigny
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Smooth Muscle Contraction ◽  
Receptor Activation ◽  
Nucleoside Triphosphate ◽  
Nucleotide Receptors ◽  
Nerve Terminals ◽  
Wild Type ◽  
Nucleoside Triphosphate Diphosphohydrolase ◽  
Bladder Contraction

Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders.

scholarly journals Role of Ca2+ in Mediating Plant Responses to Extracellular ATP and ADP

2018 ◽  
Vol 19 (11) ◽  
pp. 3590 ◽  
Author(s):  
Greg Clark ◽  
Stanley Roux
Keyword(s):  
Cytosolic Calcium ◽  
Defense Responses ◽  
Receptor Activation ◽  
Extracellular Atp ◽  
Extracellular Nucleotides ◽  
Nucleoside Triphosphate ◽  
Plant Responses ◽  
Downstream Signaling ◽  
Nucleoside Triphosphate Diphosphohydrolase

Among the most recently discovered chemical regulators of plant growth and development are extracellular nucleotides, especially extracellular ATP (eATP) and extracellular ADP (eADP). Plant cells release ATP into their extracellular matrix under a variety of different circumstances, and this eATP can then function as an agonist that binds to a specific receptor and induces signaling changes, the earliest of which is an increase in the concentration of cytosolic calcium ([Ca2+]cyt). This initial change is then amplified into downstream-signaling changes that include increased levels of reactive oxygen species and nitric oxide, which ultimately lead to major changes in the growth rate, defense responses, and leaf stomatal apertures of plants. This review presents and discusses the evidence that links receptor activation to increased [Ca2+]cyt and, ultimately, to growth and diverse adaptive changes in plant development. It also discusses the evidence that increased [Ca2+]cyt also enhances the activity of apyrase (nucleoside triphosphate diphosphohydrolase) enzymes that function in multiple subcellular locales to hydrolyze ATP and ADP, and thus limit or terminate the effects of these potent regulators.

Leishmania infantum amastigote nucleoside triphosphate diphosphohydrolase 1 (NTPDase 1): Its inhibition as a new insight into mode of action of pentamidine

2019 ◽  
Vol 200 ◽  
pp. 1-6 ◽  
Author(s):  
Ana Carolina Ribeiro Gomes Maia ◽  
Gabriane Nascimento Porcino ◽  
Michelle Lima Detoni ◽  
Leonardo Ramos Quellis ◽  
Nayara Braga Emídio ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Leishmania Infantum ◽  
Nucleoside Triphosphate ◽  
Nucleoside Triphosphate Diphosphohydrolase ◽  
Insight Into

Extracellular Adenine Nucleotide and Adenosine Metabolism in Calcific Aortic Valve Disease

2018 ◽  
Author(s):  
Barbara Kutryb-Zajac ◽  
Patrycja Jablonska ◽  
Marcin Serocki ◽  
Alicja Bulinska ◽  
Paulina Mierzejewska ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Adenine Nucleotide ◽  
Purinergic Signaling ◽  
Interstitial Cells ◽  
Valve Disease ◽  
Nucleoside Triphosphate ◽  
Extracellular Nucleotide ◽  
Calcific Aortic Valve Disease ◽  
Metabolic Pattern

AbstractExtracellular nucleotide catabolism contributes to immunomodulation, cell differentiation and tissue mineralization by controlling nucleotide and adenosine concentrations and its purinergic effects. Disturbances of purinergic signaling in valves may lead to its calcification. This study aimed to investigate the side-specific changes in extracellular nucleotide and adenosine metabolism in the aortic valve during calcific aortic valve disease (CAVD) and to identify the individual enzymes that are involved in these pathways as well as their cellular origin.Stenotic aortic valves were characterized by reduced levels of extracellular ATP removal and impaired production of adenosine. Respectively, already reduced levels of extracellular adenosine were immediately degraded further due to the elevated rate of adenosine deamination. For the first time, we revealed that this metabolic pattern was observed only on the fibrosa surface of stenotic valve that is consistent with the mineral deposition on the aortic side of the valve. Furthermore, we demonstrated that non-stenotic valves expressed mostly ecto-nucleoside triphosphate diphosphohydrolase 1 (eNTPD1) and ecto-5’nucleotidase (e5NT), while stenotic valves ecto-nucleotide pyrophosphatase/ phosphodiesterase 1, alkaline phosphatase and ecto-adenosine deaminase (eADA). On the surface of endothelial cells, isolated from non-stenotic valves, high activities of eNTPD1 and e5NT were found. Whereas, in valvular interstitial cells, eNPP1 activity was also detected. Stenotic valve immune infiltrate was an additional source of eADA. We demonstrated the presence of A1, A2a and A2b adenosine receptors in both, non-stenotic and stenotic valves with diminished expression of A2a and A2b in the former.Extracellular nucleotide and adenosine metabolism that involves complex ecto-enzyme pathways and adenosine receptor signaling were adversely modified in CAVD. In particular, diminished activities of eNTPD1 and e5NT with the increase in eADA that originated from valvular endothelial and interstitial cells as well as from immune inflitrate may affect aortic valve extracellular nucleotide concentrations to favor a proinflammatory milieu, highlighting a potential mechanism and target for CAVD therapy.

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