Ecto-Nucleotidases

Zimmermann, Herbert

doi:10.1007/978-3-662-09604-8_8

Cited by 27 publications

(42 citation statements)

References 210 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the decomposition of ATP was characterized by a delayed and transient, but not coincident production of ADP, which suggested to us that the majority of ADP was generated in the second step of a sequential enzymatic pathway. The K m value of ATP hydrolysis established by the present study, broadly lies within the range that has been previously reported in brain slices and isolated tissues [24,[32][33][34][35]36]. Although the identity of E-NTPDase isoform was not addressed in this study, the weak UDP hydrolyzing activity found in our experiments is indicative for the involvement of E-NTPDase 2 and 3, which shows a strong preference for ATP over UDP as a substrate at least in the human and in the mouse [37].…”

Section: Discussionsupporting

confidence: 57%

Extracellular Interconversion of Nucleotides Reveals an Ecto-Adenylate Kinase Activity in the Rat Hippocampus

Sperlágh

Vizi

2007

Neurochem Res

View full text Add to dashboard Cite

Here, the extracellular interconversion of nucleotides and nucleosides was investigated in rat hippocampal slices and synaptosomes by an HPLC-UV technique. Adenosine 5'-triphosphate (ATP) was converted to adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), adenosine, inosine, and hypoxanthine in the slices, whereas ADP elicited parallel and concentration-dependent formation of ATP and AMP. The specific adenylate kinase inhibitor diadenosine pentaphosphate decreased the rate of decomposition of ADP and inhibited the formation of ATP. No substantial changes in the interconversion of ADP to ATP and AMP were found in the presence of dipyridamole, flufenamic acid, the P2 receptor antagonist pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS), and the alkaline phosphatase substrate para-nitrophenylphosphate. Negligible levels of nucleotides were generated when uridine 5'-diphosphate (UDP), AMP or adenosine were used as substrates. Ecto-adenylate kinase activity was also observed in purified synaptosomes. In summary, we demonstrate the presence of an ecto-adenylate kinase activity in the hippocampus, which is a previously unrecognized pathway that influences the availability of purines in the central nervous system.

show abstract

Section: Discussionsupporting

confidence: 57%

Extracellular Interconversion of Nucleotides Reveals an Ecto-Adenylate Kinase Activity in the Rat Hippocampus

Sperlágh

Vizi

2007

Neurochem Res

View full text Add to dashboard Cite

show abstract

“…1E,F,H,I). The protein bands of 70 kDa and 677 RESEARCH ARTICLE Nucleotide signaling in adult neurogenesis 80 kDa obtained in western blots for NTPDase2 and TNAP, respectively, corresponded to the values expected for the two enzymes (Zimmermann, 2001). No immunosignals were obtained in western blots using antibodies against the related ectonucleotidases NTPDase1 and NTPDase3 and against ecto-5´-nucleotidase (not shown).…”

Section: Neurospheres Express Ecto-nucleotidasesmentioning

confidence: 81%

“…NTPDase2, previously identified on type B-cells of the adult SVZ in situ (Braun et al, 2003), preferentially hydrolyses nucleoside triphosphates. TNAP, one of the four members of the alkaline phosphatase protein family hydrolyzes extracellular nucleoside tri-, di-and monophosphates, and thus generates extracellular nucleosides (Zimmermann, 2001). TNAP is not associated with type B cells in situ (H.Z., unpublished), but it is generally associated with cultured embryonic stem cells and widely used as a marker for undifferentiated embryonic stem cells (Annerén et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…1G). As NTPDase2 has a high preference for the hydrolysis of ATP (Zimmermann, 2001), this suggested that either NTPDase2 was not present in neurospheres or that another ecto-nucleotidase predominated in the nucleotide hydrolysis. As embryonic stem cells express alkaline phosphatase (Annerén et al, 2004), an enzyme that can dephosphorylate all three nucleotides, we probed for the presence of this enzyme in the adult neurospheres.…”

Section: Neurospheres Express Ecto-nucleotidasesmentioning

confidence: 99%

“…Furthermore, we have shown that, in the adult rodent brain, the nucleoside triphosphate-hydrolyzing ecto-enzyme ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), is expressed at a high level by type B cells of the SVZ (Braun et al, 2003) and by hippocampal progenitors (Shukla et al, 2005). As ecto-nucleotidases modulate nucleotide receptor-mediated cell communication (Zimmermann, 2001), this raises the possibility that purinergic signaling is involved in the control of adult neurogenesis. Extracellular nucleotides act via ionotropic receptors (seven subtypes, P2X 1-7 , permeable to Na + , K + and Ca 2+ ) or G-protein-coupled receptors (eight subtypes, P2Y 1,2,4,6,11,12,13,14 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation

et al. 2006

View full text Add to dashboard Cite

We have previously shown that the extracellular nucleoside triphosphate-hydrolyzing enzyme NTPDase2 is highly expressed in situ by stem/progenitor cells of the two neurogenic regions of the adult murine brain: the subventricular zone (type B cells) and the dentate gyrus of the hippocampus (residual radial glia). We explored the possibility that adult multipotent neural stem cells express nucleotide receptors and investigated their functional properties in vitro. Neurospheres cultured from the adult mouse SVZ in the presence of epidermal growth factor and fibroblast growth factor 2 expressed the ecto-nucleotidases NTPDase2 and the tissue nonspecific isoform of alkaline phosphatase, hydrolyzing extracellular ATP to adenosine. ATP, ADP and, to a lesser extent, UTP evoked rapid Ca 2+ transients in neurospheres that were exclusively mediated by the metabotropic P2Y 1 and P2Y 2 nucleotide receptors. In addition, agonists of these receptors and low concentrations of adenosine augmented cell proliferation in the presence of growth factors. Neurosphere cell proliferation was attenuated after application of the P2Y 1 -receptor antagonist MRS2179 and in neurospheres from P2Y 1 -receptor knockout mice. In situ hybridization identified P2Y 1 -receptor mRNA in clusters of SVZ cells. Our results infer nucleotide receptor-mediated synergism that augments growth factor-mediated cell proliferation. Together with the in situ data, this supports the notion that extracellular nucleotides contribute to the control of adult neurogenesis.

show abstract

Ectonucleotidases: Some recent developments and a note on nomenclature

Zimmermann

2001

Drug Development Research

372

333

View full text Add to dashboard Cite

Extracellular nucleotides such as ATP, ADP, UTP, UDP, and also diadenosine polyphosphates act as signaling molecules and can be inactivated by hydrolysis via ectonucleotidases. A considerable number of surface-located enzymes can potentially be involved in the extracellular hydrolysis pathway. These include the E-NTPDase family (ectonucleoside triphosphate diphosphohydrolase family), the E-NPP family (ectonucleotide pyrophosphatase/phosphodiesterase family), ecto-5′-nucleotidase, and alkaline phosphatases. In addition, activity of ectonucleoside diphosphokinase can interconvert extracellular nucleotides, and ATP can be used as a cosubstrate of ectoprotein kinase in the phosphorylation of surface-located proteins. Members of the various ectonucleotidase families reveal overlapping substrate specificity and tissue distribution whose functional significance needs to be further elucidated. Considerable progress has been made in the past several years in characterizing novel enzyme species and their molecular and functional properties. First knock-out mice reveal insight into physiological processes governed by the activity of specific ectonucleotidases. Together this work has led to a deeper understanding of the pathways of extracellular nucleotide metabolism, including their interplay with P2 and P1 receptors or also other physiological mechanisms. Drug Dev. Res. 52:44-56, 2001.

show abstract

Ecto-Nucleotidases

Cited by 27 publications

References 210 publications

Extracellular Interconversion of Nucleotides Reveals an Ecto-Adenylate Kinase Activity in the Rat Hippocampus

Extracellular Interconversion of Nucleotides Reveals an Ecto-Adenylate Kinase Activity in the Rat Hippocampus

Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation

Ectonucleotidases: Some recent developments and a note on nomenclature

Contact Info

Product

Resources

About