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HERBERT ZIMMERMANN Y COLS. AN. R. ACAD. NAC. FARM.

Inhibition of the P2 receptors attenuates cell proliferation in spite of
the presence of mitogenic growth factors (127). Similarly, nucleotides
stimulate proliferation and dopaminergic differentiation of human
fetal midbrain neural precursor cells (128). These data provided
strong evidence that ecto-nucleotidases, nucleotides and nucleosides,
in concert with other signaling substances, can play a role in
controlling neurogenesis from resident stem cells in the adult
mammalian brain.

SYNOPSIS

Nucleotides control major physiological and pathophysiological
functions in every tissue and, due to the essentially ubiquitous
distribution of nucleotide and adenosine receptors, initiate a large
variety of cellular responses. They act as fast transmitters and,
presumably in the majority of cases, as modulators, often in
combination with other signaling molecules. Crosstalk between
nucleotide or nucleoside receptors with receptors for e.g. growth
factors has been demonstrated. This highlights the functional
significance of interactive pathways between nucleotides and other
cellular messengers. A major role of ecto-nucleotidases in these
settings is in the modulation of ligand availability for nucleotide and
nucleoside receptors. The understanding of the abundance of ecto-
nucleotidases and of their varying catalytic properties remains a
challenge but excellent examples for a cell or tissue-specific
association and function of individual enzymes have been elaborated.
Ecto-nucleotidases represent important therapeutic targets for
interfering with P2 or P1 receptor-mediated cellular signaling
pathways. The recent development of high throughput assays for
the development of ecto-nucleotidase inhibitors is expected to
considerably accelerate this long neglected aspect of nucleotide
research.

ACKNOWLEDGEMENTS

This work was supported by the Deutsche Forschungsgemein-
schaft (140/17-1).

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