Robson, Simon C.

Zimmermann, Herbert

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Simon C. Robson

Herbert Zimmermann

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Editorial
Simon C. Robson & Herbert Zimmermann
Received: 21 December 2005 /Accepted: 23 December 2005 / Published online: 5 April 2006
# Springer 2006
BMake everything as simple as possible, but not simpler’’
Albert Einstein
Nucleosides and nucleotides are primordial biological
molecules derived from glycosylamines (comprising
nucleobases and variably phosphorylated pentose sug-
ars) that serve all biological processes. These molecules
are responsible for the transmission of genetic informa-
tion and provide currency units for biological energy
transfer and generate crucial intermediates for intracel-
lular signaling processes. In keeping with Occam’s razor
and the parsimony of Nature, these ubiquitous com-
pounds are also released from cells to provide what we
consider to be integral elements of extracellular signal-
ing. Within such Bpurinergic systems’’, specificity and
regulation can be dictated by the source of the
extracellular nucleotides, expression and/or desensitiza-
tion of specific receptors for these molecular trans-
mitters and derivatives that are generated by specific
catalytic factors or ecto-enzymes. Arrays of such re-
ceptors are widely distributed in neuronal, glial, im-
mune, hepatic, bone, muscle, endothelial, epithelial and
endocrine cells and induce multiple intracellular signal-
ing cascades. To provide specificity, this process
involves at least four subtypes of P1 (adenosine)
receptors and currently over 15 subtypes of the ion
channel and G protein-coupled families of nucleotide
(P2) receptors.
Within the past decade, ecto-enzymes hydrolyzing
and interconverting extracellular nucleotides belonging
to several gene families have been discovered, then
cloned and characterized. These include our own favor-
ites, CD39 and the ecto-nucleoside triphosphate diphos-
phohydrolases (E-NTPDases). Other equally intriguing
ecto-enzymes include those of the ecto-nucleotide pyro-
phosphatase/phosphodiesterases (E-NPPs), alkaline
phosphatases, diadenosine polyphosphate hydrolases,
adenylate kinases, nucleoside diphosphate kinases,
CD38/NAD glycohydrolases (NADases), ADP-ribosyl-
transferases (ARTs) and ecto-protein kinases.
These distinct families of ecto-nucleotidases appear
to provide key components responsible for P2 receptor
modulation and functional integrity by the removal or
conversion of nucleotides to derivatives (inclusive of
nucleosides). They also dictate cellular purinergic
responses by the conversion of P2-responses to adeno-
sine-P1-mediated events with ultimate nucleoside sal-
vage by cells. These functions influence both acute,
transitory processes such as neuronal transmission or
platelet secretion and also impact upon long-term
(trophic) signaling in the control of cell proliferation,
differentiation, motility and death in tissue regenera-
tion, wound healing and cancer.
In this Special Issue of Purinergic Signalling, we
address the ensemble of key cell surface-located ecto-
enzymes. We, as guest editors, have assembled an array
of leaders in their respective fields to summarize key
areas of interest. Articles range from those detailing the
Purinergic Signalling (2006) 2:325–326
DOI 10.1007/s11302-006-9005-3
S.C. Robson (*)
Beth Israel Deaconess Medical Center,
Harvard University, Boston, MA 02215, U.S.A.
e-mail: srobson@bidmc.harvard.edu
H. Zimmermann (*)
Institut fuer Zellbiologie und Neurowissenschaft,
Biozentrum der J.W. Goeth-Universitaet,
Max-von-Loue-Str. 9, D-60438, Frankfurt am Main, Germany
e-mail: h.zimmermann@cns.uni-frankurt.de
pathophysiological significance of ecto-enzymes to
others that chiefly address structural biology and
molecular features. It is our wish that these articles
illuminate, and possibly clarify, many of the controver-
sial points in this ever enlarging and increasingly
disparate field. We also hope this issue will increase
interest in the roles of purines and pyrimidines in
physiological and pathophysiological conditions and
help provide for further acceleration of therapeutic
applications in human disease. Finally, we are grateful
to Geoffrey Burnstock for his vision in establishing this
forum and for the invitation to prepare what we believe
to be a state-of-art overview of this area.
Simon C. Robson
Harvard Medical School
Herbert Zimmermann
Biocenter, Frankfurt University
Christmas, 2005.
326 Purinergic Signalling (2006) 2:325–326


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