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VOL. 73 (2), 537-566, 2007 ECTO-NUCLEOTIDASES, MOLECULAR PROPERTIES...

recombinant soluble and catalytically active form of NTPDase1
restores postischemic cerebral perfusion and rescues from cerebral
injury (84, 124). The production of the antithrombotic metabolite
adenosine by endothelial ecto-5’-nucleotidase provides an additional
mechanism for down-regulating platelet aggregation. The functional
importance of vascular ecto-5’-nucleotidase in the formation of
extracellular adenosine from released adenine nucleotides has
recently been corroborated by the analysis of ecto-5’-nucleotidase
knockout mice (80, 125).

Adult neurogenesis: Ecto-nucleotidases are expressed on neural
progenitors and their expression pattern varies during development
of the nervous system (126). Recent work has established the
presence of stem cells in the adult mammalian brain. In the adult
murine brain, neurogenesis, the formation of new neurons from
neural progenitor cells, continuously takes place in two actively
proliferating zones, the subventricular zone (SVZ) of the lateral
ventricles and the dentate gyrus of the hippocampus. These cells
share properties of astrocytes and give rise to highly proliferating
intermediate cell types that finally mature and form neurons.
Interestingly, the ecto-ATPase NTPDase2 is highly and selectively
expressed by the stem cells (type B cells) of the SVZ (64) and by the
progenitor cells (residual radial glia) of the dentate gyrus (65). The
enzyme is no longer expressed by the progenitor cell-derived neurons.
Moreover, SVZ-derived stem cells cultured as neurospheres in the
presence of the growth factors EGF and FGF-2 express NTPDase2.
The enzyme becomes expressed in the neurogenic regions of the
rodent brain only during late gestation and thus is not involved in
embryonic neurogenesis. NTPDase2 represents a very useful and
reliable marker for the identification of adult neural stem cells.

Additional investigations revealed the expression of the tissue
non-specific form of alkaline phosphatase (TNAP) on all cell types of
the neurogenic SVZ, including stem cells, transient amplifying cells
and immature neuroblasts (D. Langer, unpublished). This imposes a
challenging scenario to the regulation of nucleotide signaling to the
densely interacting cellular elements of the neurogenic zone and
implies the functional involvement of both nucleotide and nucleoside
receptors. Indeed, neurosphere cells in vitro respond to P2 receptor
agonists and to adenosine with an increase in cell proliferation.

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