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Originally published In Press as doi:10.1074/jbc.M009527200 on December 13, 2000
J. Biol. Chem., Vol. 276, Issue 12, 8904-8909, March 23, 2001
Dinucleotides as Growth-promoting Extracellular Mediators
PRESENCE OF DINUCLEOSIDE DIPHOSPHATES Ap2A,
Ap2G, AND Gp2G IN RELEASABLE GRANULES OF
PLATELETS*
Joachim
Jankowski ,
Joost
Hagemann ,
Martin
Tepel ,
Markus
van der Giet ,
Nina
Stephan ,
Lars
Henning ,
Helena
Gouni-Berthold§,
Agapios
Sachinidis¶,
Walter
Zidek , and
Hartmut
Schlüter
From the Medizinische Klinik IV,
Universitätsklinikum Benjamin Franklin, Freie Universität
Berlin, Berlin 12200, the § Medizinische
Universitätspoliklinik, Bonn D-53111, and the ¶ Institut
für Neurophysiologie, Universität zu Köln,
Köln D-50931, Germany
Dinucleoside diphosphates,
Ap2A, Ap2G, and Gp2G
represent a new class of growth-promoting extracellular mediators,
which are released from granules after activation of platelets. The
presence of theses substances was shown after purification from a
platelet concentrate. The substances were identified by UV
spectrometry, retention time comparison with authentic substances,
matrix-assisted laser desorption/ionization mass spectrometry,
post-source-decay matrix-assisted laser desorption/ionization mass
spectrometry, and enzymatic analysis. Ap2A,
Ap2G, and Gp2G have growth-stimulating effects
on vascular smooth muscle cells in nanomolar concentrations as shown by
[3H]thymidine incorporation measurements. The calculated
EC50 (log M; mean ± S.E.) values
were 6.07 ± 0.14 for Ap2A, 6.27 ± 0.25 for
Ap2G, and 6.91 ± 0.44 for Gp2G. At
least 61.5 ± 4.3% of the dinucleoside polyphosphates are
released by platelet activation. The intraplatelet concentrations
suggest that, in the close environment of a platelet thrombus, similar
dinucleoside polyphosphate concentrations can be found as in platelets.
Intraplatelet concentration can be estimated in the range of 1/20 to
1/100 of the concentration of ATP. In conclusion, Ap2A,
Ap2G, and Gp2G derived from releasable granules
of human platelets may play a regulatory role in vascular smooth muscle
growth as growth-promoting mediators.
*
This study was supported by a grant of the Deutsche
Forschungsgemeinschaft (DFG: Schl 406/2-1).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Medizinische
Klinik IV: Nephrologie (WE 28), Universitätsklinikum Benjamin
Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany, Tel.: 49-30-8445-2441; Fax: 49-30-8445-4235;
E-mail: Hartmut.Schlueter@ruhr-uni-bochum.de.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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